Influenza virus characterization: summary report, Europe, September 2022

EE Influenza virus characterization Summary report, Europe, September 2022 WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 Document number: WHO/EURO:2022-6189-45954-67195 © World Health Organization and the European Centre for Disease Prevention and Control 2022 Some rights reserved. This work is available under the Creative Commons Attribution- 3.0 IGO licence (CC BY-3.0 IGO; Creative Commons — Attribution 3.0 IGO — CC BY 3.0 IGO). Under the terms of this licence, you may copy, redistribute and adapt the work, even commercially, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO or ECDC endorse any specific organization, products or services. The use of the WHO or ECDC logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. 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WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 3 Acknowledgments This report was prepared by Rod Daniels, Burcu Ermetal, Aine Rattigan and John McCauley (Crick Worldwide Influenza Centre) for the World Health Organization Regional Office for Europe under WHO contract. Data from The European Surveillance System – TESSy was provided by the respective country and area and released by ECDC. WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 4 _____ 1Influenza virus characterization: summary report, Europe, July 2022. World Health Organization Regional Office for Europe and European Centre for Disease Prevention and Control; Copenhagen and Stockholm; 2022 (https://apps.who.int/iris/handle/10665/363632, accessed 19 October 2022). Summary This is the ninth and final report for the 2021-2022 influenza season. The July 2022 characterisation report1, gave a breakdown of influenza detections across the World Health Organisation (WHO) European Region reported to TESSy up to week 30/2022. As of week 39/2022, 149 372 detections had been reported, resulting from extended late season influenza activity. Of these 149 372 detections, 98% were type A viruses, with A(H3N2) dominating (91%) over A(H1N1)pdm09 (9%), and 2% type B of which only 156 were ascribed to a lineage, with all but two being B/Victoria. This represents a large increase (148 096, 117-fold ) in detections compared to the 2020-2021 season, on the back of a great increase (1 957 744, 151%) in the number of samples tested. However, while there have been clear indications of an influenza epidemic in 2021-2022 with the epidemic threshold of 10% positivity within sentinel specimens having been crossed for 17 weeks (unlike in 2020-2021), numbers of detections are reduced compared to earlier seasons (e.g., 9.4% reduced compared to 2019-2020, when the number of samples tested was over 3-fold lower). The increased testing but reduced number of influenza detections is undoubtedly related to the emergence of SARS-CoV-2 and measures introduced to combat it. Five shipments from countries within the WHO European Region were received at the London WHO Collaborating Centre, the Francis Crick Worldwide Influenza Centre (WIC) since the July report. This report focuses on viruses with collection dates within 2022 for which HA gene sequences were submitted to, and released in, the EpiFluTM database of the Global Initiative on Sharing All Influenza Data (GISAID) after July 2022, together with sequences generated and antigenic data determined at the WIC. Globally relatively few A(H1N1)pdm09 viruses have been detected in the course of the 2021-2022 season. 6B.1A.5a.1 and 6B.1A.5a.2 genetic subgroups have been detected which are clearly antigenically different. 6B.1A.5a.1 viruses have been the most numerous in Europe but 6B.1A.5a.2 viruses have circulated globally and greater numbers of this subgroup have recently been detected in Europe. At the February 2022 WHO influenza vaccine composition meeting (VCM) the recommendation was to retain A/Victoria/2570/2019-like viruses (6B.1A.5a.2) as the vaccine component for the northern hemisphere 2022-2023 influenza season. At the September 2022 VCM the recommendation was to change the southern hemisphere A(H1N1)pdm09 vaccine virus for the 2023 season to an A/Sydney/5/2021-like virus as all recently circulating 6B.1A.5a.2 viruses carry HAI K54Q, A186T, Q189E, E224A, R259K and K308R amino acid substitutions compared to A/Victoria/2570/2019; while these viruses are well recognised by post-infection ferret antisera raised against A/Victoria/2570/2019, they are recognised less well by human post-vaccination sera. In Europe and across the world A(H3N2) viruses have been dominant with the vast majority of recently detected viruses falling in the ʻBangladesh-likeʼ (3C.2a1b.2a.2) subgroup, except in China where significant numbers of 3C.2a1b.2a.1 viruses have been detected. While clusters of viruses showing antigenic drift have emerged among the ʻBangladesh-likeʼ viruses, the great majority of these viruses retained good recognition by post-infection ferret antisera raised against egg-propagated A/Darwin/9/2021 (3C.2a1b.2a.2) which has been recommended for egg-based vaccines to be used in the 2022 and 2023 southern hemisphere, and 2022-23 northern hemisphere seasons. Antisera raised against a range of cell culture- and egg-propagated 3C.2a1b.2a.2 viruses generally gave good recognition of 3C.2a1b.2a.2 test viruses In Europe and across the world few B/Victoria-lineage viruses have been detected during the 2021-2022 influenza season. All fall within subclade V1A.3 represented by B/Washington/02/2019, the vaccine virus recommended for inclusion in influenza vaccines for the 2021-2022 northern hemisphere season. A large majority of HA sequences from recently detected viruses, in geographically dispersed countries, have fallen in the V1A.3a group defined by a series of HA1 amino acid substitutions including N150K, with most falling in the V1A.3a.2 subgroup with defining HA1 A127T, P144L and K203R amino acid substitutions. B/Austria/1359417/2021-like (V1A.3a.2) viruses have been recommended for use in the southern hemisphere 2022 and 2023, and the northern hemisphere 2022- 2023 influenza seasons. A B/Washington/02/2019-like (V1A.3) virus cluster that emerged and spread in the Netherlands, which showed poor recognition by the panel of post-infection ferret antisera used at the WIC, has now been detected in Spain. WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 5 Table 1 shows a summary of influenza virus detections in the WHO European Region reported to The European Surveillance System (TESSy) database during the 2021-2022 season (weeks 40/2021-39/2022), compared to the same period in the 2020-2021 season. There has been a great increase in the number of samples from patients fulfilling Influenza-Like Illness (ILI) and/or Acute Respiratory Infection (ARI) criteria being tested (1 957 744, 151%), even when compared with a more ʻnormalʼ season, 2019-2020 (2 268 305, 231%: results not shown), which led into the COVID-19 pandemic. With this increased testing there has been a rise in the number of influenza-positive samples (148 096, 117-fold), though there was a reduction compared to the same period in 2019-2020 (15 545, 9.4%: results not shown). These data probably relate to a number of factors: (i) significant numbers of samples taken from patients fulfilling ILI and/or ARI criteria being infected with other agents, possibly SARS-CoV-2, the virus responsible for the COVID-19 pandemic; (ii) residual effects of measures introduced to help curtail the spread of SARS-CoV-2, and; (iii) with large swathes of the human population now carrying a significant level of immunity to SARS-CoV-2 following either infection and/or vaccination, influenza has been able to re-establish itself after nearly two years of low-level circulation. With these caveats, and being mindful of the low number of detections during of the 2020-2021 season, the ratio of type A to type B detections has increased compared to the 2020-2021 season (1.5:1 to 51:1), with a greater dominance of A(H3N2) over A(H1N1)pdm09 viruses. While the number of influenza B virus detections has increased from 514 to 2 881 (561%), only small numbers were ascribed to a lineage in both time periods (Table 1) though, based on sequences available in GISAID, B/Yamagata lineage viruses with collection dates after March 2020 have not been characterised genetically. Currently, it appears that measures introduced relating to the COVID-19 pandemic are still having an effect but there has been clear indication of an influenza season in the Region during 2021-2022 with the rate of influenza positivity in sentinel samples having been at or above 10%, the epidemic threshold set for the Region, for 17 weeks during a bi-phasic season (weeks 49/2021 to 1/2022 and weeks 8-19/2022) with A(H3N2) viruses dominating (Figure 1). Table 1. Influenza virus detections in the WHO European Region from the start of reporting for the 2021-2022 season (weeks 40/2021-39/2022)a Figure 1. Influenza positivity in sentinel-source specimens by week (2021-2022) – WHO Europea a Figure adapted from FluNewsEurope week 36-39/2022 (https://flunewseurope.org/Archives) Sentinel sources Non-sentinel sources Totals % Ratios Sentinel sources Non-sentinel sources Totals % Ratios Influenza A 8172 138319 146491 98.1 51:1 52 710 762 59.7 1.5:1 A(H1N1)pdm09 477 3010 3487 8.8 11 33 44 15.0 A(H3N2) 6478 29882 36360 91.2 10.4:1 13 236 249 85.0 5.7:1 A not subtyped 1217 105427 106644 28 441 469 Influenza B 137 2744 2881 1.9 14 500 514 40.3 Victoria lineage 24 130 154 98.7 77:1 2 13 15 93.8 15:1 Yamagata lineage 0 2 2 1.3 0 1 1 6.2 Lineage not ascribed 113 2612 2725 12 486 498 Total detections (total tested) 8 309 (85 293) 141 063 (>3 165 913) 149 372 (>3 251 206) 66 (52 783) 1 210 (>1 240 679) 1 276 (>1 293 462) a Numbers taken from Flu News Europe to week 39/2022, week 39/2021 and week 39/2020 reports for the three influenza seasons Cumulative number of detections for weeks 40/2020-39/2021 Totals*Virus type/subtype/lineage Cumulative number of detections for weeks 40/2021-39/2022 Totals* * Percentages are shown for total detections (types A & B [in bold type], and for viruses ascribed to influenza A subtype and influenza B lineage). Ratios are given for type A:B [in bold type], A(H3N2):A(H1N1)pdm09 and Victoria:Yamagata lineages. 0 10 20 30 40 50 60 70 80 90 100 0 100 200 300 400 500 600 700 800 W ee k 20 21 -W 40 20 21 -W 41 20 21 -W 42 20 21 -W 43 20 21 -W 44 20 21 -W 45 20 21 -W 46 20 21 -W 47 20 21 -W 48 20 21 -W 49 20 21 -W 50 20 21 -W 51 20 21 -W 52 20 22 -W 01 20 22 -W 02 20 22 -W 03 20 22 -W 04 20 22 -W 05 20 22 -W 06 20 22 -W 07 20 22 -W 08 20 22 -W 09 20 22 -W 10 20 22 -W 11 20 22 -W 12 20 22 -W 13 20 22 -W 14 20 22 -W 15 20 22 -W 16 20 22 -W 17 20 22 -W 18 20 22 -W 19 20 22 -W 20 20 22 -W 21 20 22 -W 22 20 22 -W 23 20 22 -W 24 20 22 -W 25 20 22 -W 26 20 22 -W 27 20 22 -W 28 20 22 -W 29 20 22 -W 30 20 22 -W 31 20 22 -W 32 20 22 -W 33 20 22 -W 34 20 22 -W 35 20 22 -W 36 20 22 -W 37 20 22 -W 38 20 22 -W 39 % p os iti ve N um be r o f po si tiv e sp ec im en s Year-week B A(H3) A(H1)pdm09 A unsubtyped % positive WHO European Region Epidemic Threshold (10%) No cases of infection with circulating B/Yamagata-lineage viruses have been confirmed since March of 2020. All HA gene sequences from the 77 viruses detected in 2020, inclusive of 16 from the WHO European Region, belonged to genetic clade Y3 and had three HA1 amino acid substitutions (L172Q, D229N and M251V) compared to B/Phuket/3073/2013-like viruses which are still recommended for use in quadrivalent influenza vaccines. There is need to share all B/Yamagata-lineage viruses detected recently for detailed characterisation to determine if there are any in circulation that are not related to Live Attenuated Influenza Vaccines. WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 6 Genetic and antigenic characterisation data generated at the WIC for viruses with collection dates after 31 August 2020 until 31 January 2021, up to a report deadline of 15 February 2021, contributed to the WIC virus characterisation report that was presented at the WHO influenza vaccine composition meeting (VCM) in February 2021 when recommendations were made for the northern hemisphere 2021-2022 season [1]. Data generated on viruses with collection dates after 31 January 2021 until 31 August 2021 informed the September 2021 VCM when recommendations were made for the 2022 southern hemisphere season [2]. Data presented for viruses with collection dates after 31 August 2021 until 31 January 2022 contributed to the VCM (21-24 February) where it was recommended to change the A(H3N2) and B/Victoria-lineage components of influenza vaccines to match those used in 2022 southern hemisphere vaccination campaigns [3]. At the recent VCM (19-22 September), which focussed on data from viruses collected after 31 January 2022 until 31 August 2022, it was recommended to change the A(H1N1)pdm09 vaccine component for the 2023 southern hemisphere season [4]. Due to the relatively low number of influenza-positive specimens detected until recently, and thereby available for sharing with WIC, this and recent influenza characterisation reports (https://www.ecdc.europa.eu/en/seasonal- influenza/surveillance-and-disease-data/influenza-virus-characterisation) have been based mainly on phylogenetic analyses of complete HA gene sequences submitted to GISAIDʼs EpiFluTM database, inclusive of sequences generated at the WIC. Here A(H1N1)pdm09, A(H3N2) and B/Victoria-lineage HA gene phylogenies for viruses with collection dates after 31 December 2021, for representative WIC- and non-WIC-generated sequences available in GISAID, generated for the July report are presented (Figures 2a, 3a and 4a). Additional phylogenies (Figures 2b, 3b and 4b) are presented for HA sequences derived from viruses with collection and HA sequence submission dates from the days indicated in Table 2, with a sequence download date of 28 September 2022. The numbers of HA sequences, downloaded from GISAID, numbers remaining after de-duplication and the numbers used in the new representative phylogenies generated for this September report are shown. Table 2. Summary of the numbers of HA gene sequences available and used in generating the new phylogenies presented in this report Eighty-nine shipments of specimens (virus isolates and/or clinical specimens) were received at the WIC from WHO Global Influenza Surveillance and Response System (GISRS) recognised National Influenza Centres (NICs) in a total of 39 WHO European Region Member States (Table 3). Of the 2 342 samples received 2 209 (94%) were type A viruses and 133 (6%) were type B viruses. Five of the shipments were received in August through September 2022 and contained samples from the second phase of the epidemic (Figure 1), a number of which are still in the virus characterization process (Table 3). NICs were requested to send clinical specimens with real-time RTPCR Ct values of ≤30 and/or virus isolates, all those available for A(H1N1)pdm09 and influenza type B (as relatively few have been detected), and a representative selection of A(H3N2) samples. A total of 139 viruses from the WHO European Region, 24 A(H1N1)pdm09, 97 A(H3N2) and 18 B/Victoria-lineage, have been characterised antigenically since the July report (Tables 4, 5 and 6 respectively). Virus collection date (from) Sequence submission date (from) Number Downloaded Number de-duplicated and aligned Number used in phylogenies* A(H1N1)pdm09 2022-06-01 2022-08-01 223 203 203 A(H3N2) 2022-08-01 2022-08-01 226 226 226 B/Victoria 2022-03-01 2022-08-01 217 213 213 B/Yamagata 2022-01-01 2022-08-01 0 0 0 * Inclusive of sequences generated recently at the WIC, but not including sequences from reference and vaccine viruses Virus subtype/lineage Global HA sequences available for viruses collected in the 2021-2022 season as of 2022-09-28 WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 7 Table 3. Summary of seasonal influenza clinical samples and virus isolates* with collection dates after 2021-08-31 contained in packages received from WHO European Region Member States MONTH TOTAL RECEIVED Seasonal Number Number Number Number Number Number Number Number Number Number Number viruses received propagated1 received propagated1 received received propagated1 received propagated1 received propagated1 2021 September Belgium 1 1 1 Croatia 3 3 2 0 Denmark 5 5 5 France 11 1 0 10 9 0 Israel 2 2 2 Italy 1 1 1 0 Netherlands 13 12 12 1 1 Spain 1 1 0 0 Sweden 2 1 1 1 1 the United Kingdom (England) 2 2 2 October Denmark 2 1 1 1 1 0 Estonia 1 1 0 0 France 12 9 8 3 3 Germany 2 2 2 Ireland 1 1 1 Italy 5 3 3 2 2 Kyrgyzstan 28 28 0 0 Netherlands 36 36 17 0 Norway 7 7 7 Portugal 3 2 0 0 1 0 Russian Federation 3 3 3 Spain 4 4 3 0 Sweden 2 2 2 Tajikistan 7 6 0 1 1 the United Kingdom (England) 8 8 8 the United Kingdom (Scotland) 5 1 4 November Armenia 2 2 0 0 Belgium 2 2 2 Croatia 1 1 1 Estonia 1 1 0 0 France 29 19 in process 10 8 0 Germany 5 4 4 1 1 Ireland 3 2 0 0 1 1 Ireland 1 1 Israel 10 10 6 0 Italy 5 5 5 Kazakhstan 13 13 0 0 Kyrgyzstan 22 22 0 0 Netherlands 24 24 20 0 Norway 8 8 5 0 Romania 1 1 1 Russian Federation 36 36 35 0 Slovenia 2 2 1 0 Spain 36 1 1 33 10 0 1 0 1 0 Sweden 5 5 5 Switzerland 4 2 2 2 2 Tajikistan 8 7 0 1 0 the United Kingdom (Scotland) 2 2 the United Kingdom (N. Ireland) 3 2 1 Kosovo$ 2 2 1 0 December Albania 39 1 0 3 3 35 10 0 Armenia 21 21 10 0 Belgium 15 1 0 7 6 7 2 0 Bosnia and Herzegovina 3 3 0 0 Croatia 7 1 1 6 5 0 Estonia 7 7 1 0 France 8 4 in process 4 in process Georgia 11 1 0 9 4 0 1 0 Germany 10 10 10 Hungary 2 2 2 Ireland 4 1 0 3 3 0 Ireland 1 1 Israel 30 30 5 0 Kazakhstan 17 17 2 0 Latvia 5 5 5 Montenegro 6 6 1 0 Netherlands 29 5 5 24 23 1 Norway 1 1 1 Portugal 18 1 0 14 3 0 1 0 2 1 Romania 5 5 5 Russian Federation 5 5 5 Serbia 7 5 0 2 1 0 Slovenia 1 1 1 Spain 57 4 2 52 10 0 1 0 Switzerland 10 1 0 9 6 0 Ukraine 14 14 in process Kosovo$ 56 3 0 5 0 48 7 0 2022 January Armenia 2 2 1 0 Belgium 19 10 9 9 2 0 Bosnia and Herzegovina 5 5 0 0 Bulgaria 8 8 8 Estonia 4 4 4 France 3 3 3 Georgia 4 4 2 0 Germany 11 11 11 Hungary 2 2 2 Ireland 2 2 0 0 Ireland 2 1 1 Israel 9 9 0 0 Italy 1 1 1 Latvia 1 1 1 Montenegro 8 2 0 6 1 0 Netherlands 6 3 3 3 3 Norway 10 1 0 9 4 0 Portugal 7 7 0 0 Romania 4 1 1 3 3 Russian Federation 3 3 3 Serbia 21 21 11 0 Slovenia 2 2 1 0 Spain 16 13 3 3 3 Switzerland 7 1 1 6 4 0 Ukraine 21 21 9 0 Kosovo$ 2 1 0 1 0 0 As of 2022-10-02 Some samples are RNA, so only genetic characterisation possible Some samples not cultured because Ct value high (>30), failed sequence, identical sequence, mixed sequence or SARS-COV-2 positive Some samples not cultured because when received they were too old for consideration at the September 2022 VCM $ All references to Kosovo in this document should be understood to be in the context of the United Nations Security Council resolution 1244 (1999). 1. Propagated to sufficient titre to perform HI assay (the totalled number does not include any from batches that are in process) * Note: Where clinical sample and a virus isolate from the same patient were received, this is counted as one in the Total Received and following columns. 2. Propagated to sufficient titre to perform HI assay in the presence of 20nM oseltamivir (the totalled number does not include any from batches that are in process) Numbers in red indicate viruses recovered but with insufficient HA titre to permit HI assay (H3N2 only) Samples provided in lysis buffer, so only genetic characterisation possible Country/area Number propagated2 B Yamagata lineageA H1N1pdm09 H3N2 B B Victoria lineage WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 8 MONTH TOTAL RECEIVED Seasonal Number Number Number Number Number Number Number Number Number Number Number viruses received propagated1 received propagated1 received received propagated1 received propagated1 received propagated1 FEBRUARY Austria 3 1 1 2 2 Belgium 15 5 5 10 1 0 Bosnia and Herzegovina 1 1 0 Bulgaria 4 4 4 Croatia 2 2 0 0 Denmark 1 1 1 Estonia 4 3 2 0 1 1 France 8 4 2 4 4 Germany 12 1 1 11 11 Hungary 3 3 3 Italy 6 1 1 5 5 Moldova 1 1 1 Netherlands 4 3 3 1 1 Norway 2 2 2 Poland 1 1 1 Portugal 32 1 0 31 23 0 Slovakia 1 1 0 0 Slovenia 12 12 12 Spain 12 2 1 10 10 Sweden 2 2 2 Switzerland 4 4 3 Ukraine 1 1 1 MARCH Austria 27 4 4 23 21 0 Belgium 91 16 14 75 18 0 Bosnia and Herzegovina 2 2 0 0 Bulgaria 16 16 16 Croatia 12 12 1 0 Denmark 12 1 1 11 11 France 18 8 7 10 in process Germany 8 1 1 7 7 Hungary 4 4 4 Iceland 4 4 0 0 Ireland 39 39 4 0 Italy 12 2 2 10 10 Kyrgyzstan 6 6 6 Lithuania 1 1 0 0 Moldova 7 2 2 5 5 Montenegro 19 19 4 0 Netherlands 12 4 4 4 4 4 4 Norway 20 2 1 16 13 0 2 2 Poland 27 2 0 25 15 0 Portugal 10 10 8 0 Romania 1 1 0 Russian Federation 3 3 3 Serbia 13 4 1 9 7 0 Slovakia 2 2 0 0 Slovenia 40 40 39 0 Spain 31 5 3 26 26 Sweden 7 4 4 3 3 Switzerland 20 6 6 14 13 0 Ukraine 3 2 1 0 1 0 the United Kingdom (N. Ireland) 3 3 APRIL Austria 23 1 1 22 13 0 Belgium 19 4 4 15 14 0 Bosnia and Herzegovina 5 5 3 0 Bulgaria 3 3 2 0 Croatia 37 37 6 1 Denmark 8 6 6 2 2 Estonia 26 26 24 0 France 12 3 2 8 in process 1 1 Germany 8 2 2 6 6 Hungary 2 2 2 Iceland 27 2 0 25 1 0 Ireland 11 1 1 10 3 0 Italy 14 13 12 0 1 1 Kyrgyzstan 6 6 6 Latvia 15 2 2 12 12 1 0 Lithuania 46 46 7 0 Moldova 7 1 2 6 6 Montenegro 6 6 1 0 Netherlands 27 1 1 6 5 0 20 16 Norway 38 10 10 25 21 0 3 1 Poland 64 5 0 45 19 0 3 0 11 5 Portugal 10 10 10 Romania 28 4 4 24 24 Russian Federation 8 8 8 Serbia 11 5 2 4 4 2 2 Slovakia 7 7 0 0 Slovenia 11 11 11 Spain 60 5 4 54 9 0 1 1 Sweden 9 1 1 7 7 1 1 Switzerland 14 2 0 12 6 0 Ukraine 3 2 2 1 1 the United Kingdom (N. Ireland) 24 24 MAY Austria 2 2 2 Belgium 2 1 1 1 1 Bosnia and Herzegovina 1 1 0 0 Croatia 3 3 3 Denmark 3 2 2 1 1 France 6 1 1 4 4 1 1 Germany 11 1 1 8 8 2 2 Iceland 18 18 1 0 Italy 1 1 1 Lithuania 2 2 2 Netherlands 2 2 0 Norway 3 3 3 Poland 9 7 6 0 1 0 1 1 Portugal 7 3 3 4 4 Romania 9 1 1 5 4 0 3 2 Russian Federation 4 4 4 Serbia 5 1 0 4 3 Spain 50 2 0 48 29 0 Sweden 1 1 1 Ukraine 1 1 1 JUNE Croatia 1 1 1 Denmark 1 1 1 France 2 2 2 Norway 5 3 3 2 2 Romania 2 2 2 Russian Federation 1 1 1 Spain 5 1 0 4 2 0 the United Kingdom (N. Ireland) 6 1 4 1 JULY Croatia 2 1 1 1 0 0 France 11 1 1 10 10 Norway 12 1 0 10 8 0 1 0 AUGUST Norway 3 1 1 2 0 TOTAL 2342 33 0 252 172 1924 1023 2 10 0 119 93 4 0 39 Countries/areas As of 2022-10-02 Numbers in red indicate viruses recovered but with insufficient HA titre to permit HI assay (H3N2 only) Samples provided in lysis buffer, so only genetic characterisation possible Some samples are RNA, so only genetic characterisation possible Some samples not cultured because Ct value high (>30), failed sequence, identical sequence, mixed sequence or SARS-COV-2 positive Some samples not cultured because when received they were too old for consideration at the September 2022 VCM $ All references to Kosovo in this document should be understood to be in the context of the United Nations Security Council resolution 1244 (1999). 1. Propagated to sufficient titre to perform HI assay (the totalled number does not include any from batches that are in process) 2. Propagated to sufficient titre to perform HI assay in the presence of 20nM oseltamivir (the totalled number does not include any from batches that are in process) 0.4% 5.1% 0.2% 94.3% 5.7% * Note: Where clinical sample and a virus isolate from the same patient were received, this is counted as one in the Total Received and following columns. Country/area Number propagated2 1.4% 10.8% 82.2% B Yamagata lineageA H1N1pdm09 H3N2 B B Victoria lineage WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 9 Influenza A(H1N1)pdm09 virus analyses All recently circulating viruses have fallen into clade 6B.1A, defined by the amino acid substitutions S74R, S84N, S162N (introducing a potential N-linked glycosylation site), S164T (which alters the glycosylation motif at residues 162 to 164), I216T and I295V in HA1. Within clade 6B.1A, clusters of viruses (genetic groups) encoding a range of HA amino acid substitutions have emerged, with most recently circulating viruses carrying the substitution S183P in HA1, although this is not retained in all genetic groups. Figures 2a and 2b are annotated with HA1 S183P substitution groups assigned for the February 2019 WHO VCM, updated for the September 2020 WHO VCM, and with a new nomenclature introduced at the time of the September 2021 WHO VCM (6B.1A.1 to 6B.1A.7). The recommended vaccine viruses for the northern hemisphere 2021-2022 and 2022-2023, and southern hemisphere 2022 (egg-based A/Victoria/5270/2019-like and cell-based A/Wisconsin/588/2019-like) influenza seasons are shown in red [1, 3, 2] as is the case for the recent recommendation for the southern hemisphere2023 season, egg- and cell- based A/Sydney/5/2021-like [4]. The seven subclades are defined by the following HA amino acid substitutions: 1. Subclade 6B.1A.1 viruses, represented by the 2019-2020 vaccine virus A/Brisbane/02/2018, carry an HA gene mutation encoding HA1 S183P amino acid substitution. 2. Subclade 6B.1A.2 viruses, represented by A/Denmark/2728/2019, carry HA gene mutations encoding HA1 S183P and L233I with HA2 V193A amino acid substitutions – a group within this subclade has emerged with additional HA1 amino acid substitutions of N129D, K130N, P137S, N156K and K211R (e.g. A/Hong Kong/110/2019). 3. Subclade 6B.1A.3 viruses, represented by A/Norway/3737/2018, carry HA gene mutations encoding HA1 T120A and S183P amino acid substitutions. 4. Subclade 6B.1A.4 represented by A/Hungary/20/2018 carries HA gene mutations encoding HA1 N129D, A144E and S183P amino acid substitutions. 5. Subclade 6B.1A.5 viruses carry HA gene mutations encoding HA1 S183P and N260D amino acid substitutions and split into two groups designated 6B.1A.5a represented by A/Norway/3433/2018 with additional HA1 amino acid substitutions of N129D and T185A, and 6B.1A.5b represented by A/Switzerland/3330/2017 with additional amino acid substitutions of HA1 E235D and HA2 V193A. Two subgroups within the 6B.1A.5a group have been defined based on HA1 amino acid substitutions of D187V/A and Q189E (6B.1A.5a.1) or K130N, N156K, L161I and V250A (6B.1A.5a.2). 6. Subclade 6B.1A.6 viruses, represented by A/Ireland/84630/2018, carry HA gene mutations encoding HA1 T120A and S183P amino acid substitutions, like subclade 6B.1A.3 viruses, but fall within a separate phylogenetic branch which is closer to subclade 6B.1A.5 viruses. 7. Subclade 6B.1A.7 viruses, represented by A/Slovenia/1489/2019, carry HA gene mutations encoding HA1 K302T and HA2 I77M, N169S and E179D amino acid substitutions sometimes with additional HA1 substitutions of E68D, S121N and L161I (e.g. A/Moscow/193/2019). Note: a group within this subclade has emerged with P183S (reversion), T185I, I240V and I286L substitutions in HA1 (e.g. A/Estonia/120012/2019). The phylogeny prepared for the July report focused on HA sequences derived from viruses with collection dates after 30 April 2022 for which sequences were submitted to GISAID after June 2022. Of the 19 sequences derived from viruses detected in the WHO European Region, 17 fell in subgroup 6B.1A.5a.1 and two in subgroup 6B.1A.5a.2 (Figure 2a). Sequences derived from small numbers of 6B.1A.5a.1 viruses recently detected in Australia, South Africa and the USA were also reported. Subgroup 6B.1A.5a.2 viruses continued to dominate in countries outside of the WHO European Region, notably those in the southern hemisphere. The phylogeny prepared for this September report focused on HA sequences derived from viruses with collection dates after 31 May 2022 for which sequences were submitted to GISAID after July 2022 (Table 2). As indicated in both phylogenies, recently detected viruses in subgroup 6B.1A.5a.2 all have HA1 K54Q, A186T, Q189E, E224A, R259K and K308R substitutions compared to the vaccine virus, A/Victoria/2570/2019 (Figures 2a and 2b) and virus clusters have emerged defined by amino acid substitutions: (i) HA1 T216A often with D94N , the cluster showing wide geographic distribution; (ii) HA1 A48P, and; (iii) HA1 K142R, D260E and HA2 I91V, N124H, often with HA1 P137S, T277A and HA2 E29D. Viruses in cluster (iii) with the additional substitutions have recently been detected in countries of the WHIO European Region (Croatia, Germany, Netherlands, Norway, Spain, Sweden and the United Kingdom; Figure 2b). The panel of post-infection ferret antisera used in HI assays, five raised against subgroup 6B.1A.5a.1 viruses and three against 6B.1A.5a.2 viruses, gives clear discrimination of test viruses in the two subgroups (Tables 4-1 and 4-2). Of the 21 6B.1A.5a.1 test viruses, 19 (90%), 21 (100%), 19 (90%), 21 (100%) and 20 (95%) were recognised well (within fourfold of the homologous titres) by antisera raised against A/Ireland/87733/2019, cell culture- and egg- WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 10 propagated A/Guangdong-Maonan/SWL1536/2019 (vaccine viruses for the 2020-2021 northern hemisphere season), A/Ghana/1894/2021 and A/Lyon/820/2021, respectively. The three 6B.1A.5a.2 test viruses from Norway were all recognised well (within twofold of the homologous titres) by antisera raised against three different 6B.1A.5a.2 reference viruses. This included the vaccine virus (IVR-215: A/Victoria/2570/2019) for the 2021-2022 northern hemisphere season and indicates that a variety of genetically clustered viruses, defined by specific HA1 amino acid substitutions, cannot be discriminated antigenically by the post-infection ferret antisera used in HI assays. At the WHO VCM held in Geneva 21-24 February 2022, A/Victoria/2570/2019-like viruses were recommended for use in the northern hemisphere 2022-2023 influenza season [3]. This decision was largely based on antisera induced by 6B.1A.5a.1 subgroup viruses in ferrets and humans yielding poor recognition of 6B.1A.5a.2 subgroup viruses and the likelihood that many humans were unlikely to have been exposed to 6B.1A.5a.2 subgroup viruses given their low-level circulation during the COVID-19 pandemic. While the different clusters of 6B.1A.5a.2 subgroup viruses were not differentiated by post-infection ferret antisera, human serology data presented at the WHO VCM held in Dublin 19-22 September 2022 indicated poor recognition of many 6B.1A.5a.2 subgroup viruses. For this reason, egg- and cell culture-propagated A/Sydney/5/2021-like viruses, carrying the HA1 K54Q, A186T, Q189E, E224A, R259K and K308R substitutions compared to A/Victoria/2570/2019, were recommended for vaccine formulations to be used in the 2023 southern hemisphere season [4]. WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 11 Figure 2a. Phylogenetic comparison of influenza A(H1N1)pdm09 HA genes (GISAID/WIC, July 2022) WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 12 Figure 2b. Phylogenetic comparison of influenza A(H1N1)pdm09 HA genes (GISAID/WIC, Sept 2022) WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 13 Table 4-1. Antigenic analysis of influenza A(H1N1)pdm09 viruses by HI V iru se s O th er C ol le ct io n Pa ss ag e A/ Ire A/ G -M A/ G -M A/ G ha na A/ Ly on A/ D en m ar k IV R -2 15 A/ Sy dn ey in fo rm at io n da te h is to ry 87 73 3/ 19 SW L1 53 6/ 19 SW L1 53 6/ 19 18 94 /2 1 82 0/ 21 32 80 /1 9 A/ Vi c/ 25 70 /1 9 5/ 21 Pa ss ag e hi st or y Eg g M D C K Eg g Eg g Eg g M D C K Eg g Eg g Fe rr et n um be r St J ud e' s F1 8/ 20 *1 F0 9/ 20 *1 F1 2/ 20 *1 F0 2/ 22 *1 F0 6/ 22 *1 F2 8/ 20 *1 F3 7/ 21 *1 F0 4/ 22 *1 G en et ic g ro up 6B .1 A. 5a .1 6B .1 A. 5a .1 6B .1 A. 5a .1 6B .1 A. 5a .1 6B .1 A. 5a .1 6B .1 A. 5a .2 6B .1 A. 5a .2 6B .1 A. 5a .2 R EF ER EN C E VI R U SE S A/ Ire la nd /8 77 33 /2 01 9 6B .1 A. 5a .1 20 19 -1 1- 03 E4 64 0 12 80 12 80 64 0 32 0 40 80 40 A/ G ua ng do ng -M ao na n/ SW L1 53 6/ 20 19 6B .1 A. 5a .1 20 19 -0 6- 17 C 2/ M D C K 1 64 0 12 80 12 80 12 80 32 0 80 80 40 A/ G ua ng do ng -M ao na n/ SW L1 53 6/ 20 19 6B .1 A. 5a .1 20 19 -0 6- 17 E3 /E 2 32 0 12 80 12 80 64 0 16 0 40 80 40 A/ G ha na /1 89 4/ 20 21 6B .1 A. 5a .1 20 21 -0 7- 21 E2 /E 1 64 0 25 60 25 60 12 80 32 0 80 16 0 80 A/ Ly on /8 20 /2 02 1 6B .1 A. 5a .1 20 21 -1 1- 16 E1 /E 2 80 32 0 32 0 16 0 64 0 40 40 40 A/ D en m ar k/ 32 80 /2 01 9 6B .1 A. 5a .2 20 19 -1 1- 10 M D C K 4/ M D C K 5 40 40 80 < 80 12 80 12 80 12 80 IV R -2 15 (A /V ic to ria /2 57 0/ 20 19 ) 6B .1 A. 5a .2 20 18 -1 1- 22 E4 /D 7/ E2 40 80 80 80 80 64 0 12 80 12 80 A/ Sy dn ey /5 /2 02 1 6B .1 A. 5a .2 E3 /E 1 40 80 40 40 40 12 80 12 80 12 80 TE ST V IR U SE S A/ To ur s/ 37 55 4/ 20 21 6B .1 A. 5a .1 20 21 -1 1- 02 M D C K 1 64 0 12 80 12 80 64 0 32 0 40 80 40 A/ D ijo n/ 48 65 8/ 20 21 6B .1 A. 5a .1 20 21 -1 2- 08 M D C K 2 64 0 12 80 12 80 64 0 16 0 40 80 80 A/ Al sa ce /4 89 17 /2 02 1 6B .1 A. 5a .1 20 21 -1 2- 15 M D C K 1 64 0 12 80 12 80 12 80 32 0 40 80 80 A/ Ile d e Fr an ce /5 21 32 /2 02 1 6B .1 A. 5a .1 20 21 -1 2- 27 M D C K 1 64 0 12 80 12 80 64 0 16 0 40 80 80 A/ Ile d e Fr an ce /5 44 52 /2 02 1 6B .1 A. 5a .1 20 22 -0 1- 03 M D C K 1 64 0 12 80 12 80 64 0 32 0 40 80 40 A/ Ly on /2 15 /2 02 2 6B .1 A. 5a .1 20 22 -0 1- 24 M D C K x/ M D C K 1 80 32 0 16 0 32 0 80 16 0 32 0 16 0 A/ C le rm on t-F er ra nd /1 84 /2 02 2 6B .1 A. 5a .1 20 22 -0 1- 25 M D C K x/ M D C K 1 32 0 12 80 12 80 64 0 16 0 40 40 40 A/ Pa ris /1 01 05 /2 02 2 6B .1 A. 5a .1 20 22 -0 2- 03 M D C K 1 32 0 64 0 12 80 64 0 16 0 40 80 40 A/ Le M an s/ 15 00 6/ 20 22 6B .1 A. 5a .1 20 22 -0 2- 24 M D C K 1 64 0 12 80 12 80 12 80 32 0 80 80 80 A/ G re no bl e/ 46 5/ 20 22 6B .1 A. 5a .1 20 22 -0 3- 02 M D C K x/ M D C K 1 64 0 12 80 12 80 12 80 32 0 40 80 80 A/ B el gi um /S 04 97 /2 02 2 6B .1 A. 5a .1 20 22 -0 3- 07 M D C K 1/ M D C K 2 64 0 12 80 25 60 12 80 32 0 80 80 40 A/ R om an s/ 47 8/ 20 22 6B .1 A. 5a .1 20 22 -0 3- 14 M D C K x/ M D C K 1 64 0 12 80 12 80 64 0 16 0 40 80 40 A/ Ly on /6 14 /2 02 2 6B .1 A. 5a .1 20 22 -0 3- 21 M D C K x/ M D C K 1 64 0 12 80 12 80 64 0 16 0 40 80 80 A/ Ly on /5 72 /2 02 2 6B .1 A. 5a .1 20 22 -0 3- 21 M D C K x/ M D C K 1 32 0 12 80 12 80 64 0 16 0 40 80 40 A/ Ly on /C H U -R .2 2. 17 2. 23 /2 02 2 N 15 6S , N 16 2* (- ch o) 6B .1 A. 5a .1 20 22 -0 3- 27 M D C K 2/ M D C K 1 80 64 0 16 0 32 0 16 0 40 80 80 A/ To ul on /7 59 /2 02 2 6B .1 A. 5a .1 20 22 -0 3- 27 M D C K x/ M D C K 1 64 0 12 80 12 80 64 0 16 0 40 80 80 A/ D un ke rq ue /2 66 98 /2 02 2 6B .1 A. 5a .1 20 22 -0 3- 31 M D C K 2 64 0 12 80 25 60 12 80 32 0 80 80 40 A/ Ly on /C H U -R 22 .2 24 .1 2/ 20 22 6B .1 A. 5a .1 20 22 -0 4- 25 M D C K x/ M D C K 1 32 0 12 80 12 80 64 0 16 0 40 80 80 A/ Ly on /C H U -R 22 .2 42 .3 4/ 20 22 6B .1 A. 5a .1 20 22 -0 5- 09 M D C K x/ M D C K 1 64 0 12 80 12 80 64 0 32 0 40 80 80 *S up er sc rip ts re fe r t o an tis er um p ro pe rt ie s (< re la te s to th e lo w es t d ilu tio n of a nt is er um u se d) Va cc in e Va cc in e Va cc in e 1 < = < 40 ; 2 < = < 80 ; N D = N ot D on e N H 2 02 0- 21 SH 2 02 1 SH 2 02 3 N H 2 02 1- 22 SH 2 02 2 N H 2 02 2- 23 H ae m ag gl ut in at io n in hi bi tio n tit re Po st -in fe ct io n fe re re t a nt is er a WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 14 Table 4-2. Antigenic analysis of influenza A(H1N1)pdm09 viruses by HI N EW N EW Vi ru se s O th er C ol le ct io n Pa ss ag e A/ Ire A/ G -M A/ G -M A/ G ha na A/ G ha na A/ Ly on A/ D en m ar k IV R -2 15 A/ Sy dn ey A/ Sy dn ey in fo rm at io n da te h is to ry 87 73 3/ 19 SW L1 53 6/ 19 SW L1 53 6/ 19 18 94 /2 1 18 94 /2 1 82 0/ 21 32 80 /1 9 A/ Vi c/ 25 70 /1 9 5/ 21 5/ 21 Pa ss ag e hi st or y Eg g M D C K Eg g Eg g Eg g Eg g M D C K Eg g Eg g Eg g Fe rr et n um be r St J ud e' s F1 8/ 20 *1 F0 9/ 20 *1 F1 2/ 20 *1 F0 2/ 22 *1 F3 5/ 22 *1 F0 6/ 22 *1 F2 8/ 20 *1 F3 7/ 21 *1 F0 4/ 22 *1 F3 4/ 22 *1 G en et ic g ro up 6B .1 A. 5a .1 6B .1 A. 5a .1 6B .1 A. 5a .1 6B .1 A. 5a .1 6B .1 A. 5a .1 6B .1 A. 5a .1 6B .1 A. 5a .2 6B .1 A. 5a .2 6B .1 A. 5a .2 6B .1 A. 5a .2 R EF ER EN C E VI R U SE S A/ Ire la nd /8 77 33 /2 01 9 6B .1 A. 5a .1 20 19 -1 1- 03 E4 12 80 25 60 25 60 12 80 12 80 32 0 40 80 80 40 A/ G ua ng do ng -M ao na n/ SW L1 53 6/ 20 19 6B .1 A. 5a .1 20 19 -0 6- 17 C 2/ M D C K 1 12 80 25 60 25 60 12 80 12 80 32 0 80 80 80 40 A/ G ua ng do ng -M ao na n/ SW L1 53 6/ 20 19 6B .1 A. 5a .1 20 19 -0 6- 17 E3 /E 2 64 0 12 80 12 80 64 0 64 0 32 0 40 80 40 40 A/ G ha na /1 89 4/ 20 21 6B .1 A. 5a .1 20 21 -0 7- 21 E2 /E 1 64 0 12 80 25 60 12 80 12 80 32 0 80 16 0 80 80 A/ Ly on /8 20 /2 02 1 6B .1 A. 5a .1 20 21 -1 1- 16 E1 /E 2 16 0 32 0 32 0 16 0 16 0 32 0 40 40 40 < A/ D en m ar k/ 32 80 /2 01 9 6B .1 A. 5a .2 20 19 -1 1- 10 M D C K 4/ M D C K 5 40 80 80 < 40 40 12 80 12 80 12 80 64 0 IV R -2 15 (A /V ic to ria /2 57 0/ 20 19 ) 6B .1 A. 5a .2 20 18 -1 1- 22 E4 /D 7/ E2 40 16 0 80 40 40 80 64 0 12 80 64 0 32 0 A/ Sy dn ey /5 /2 02 1 6B .1 A. 5a .2 E3 /E 1 80 80 80 40 40 40 12 80 12 80 12 80 12 80 TE ST V IR U SE S A/ Lo rr ai ne /2 86 57 /2 02 2 6B .1 A. 5a .1 20 22 -0 4- 11 M D C K 3 32 0 64 0 64 0 64 0 32 0 16 0 40 40 40 < A/ N or w ay /2 38 77 /2 02 2 6B .1 A. 5a .1 20 22 -0 6- 04 M D C K 1 64 0 12 80 12 80 12 80 40 16 0 40 < 40 64 0 A/ N or w ay /2 50 89 /2 02 2 6B .1 A. 5a .2 20 22 -0 6- 15 M D C K 1 < < < < < < 64 0 12 80 64 0 64 0 A/ N or w ay /2 50 93 /2 02 2 6B .1 A. 5a .2 20 22 -0 6- 15 M D C K 1 < 40 < < < < 64 0 12 80 64 0 64 0 A/ N or w ay /2 94 26 /2 02 2 6B .1 A. 5a .2 20 22 -0 8- 02 M D C K 1 < 80 40 < < < 25 60 25 60 25 60 25 60 *S up er sc rip ts re fe r t o an tis er um p ro pe rt ie s (< re la te s to th e lo w es t d ilu tio n of a nt is er um u se d) Va cc in e Va cc in e 1 < = < 40 ; 2 < = < 80 ; N D = N ot D on e N H 2 02 0- 21 SH 2 02 1 N H 2 02 1- 22 SH 2 02 2 N H 2 02 2- 23 H ae m ag gl ut in at io n in hi bi tio n tit re Po st -in fe ct io n fe rr et a nt is er a Va cc in e SH 2 02 3 WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 15 Influenza A(H3N2) virus analyses A(H3N2) viruses with HA sequences in clade 3C.2a have been dominant since the 2014-15 influenza season with group 3C.2a1b viruses predominating over the course of the 2019-2020 season in most WHO-defined regions of the world but for the European Region where there was equivalence of clade 3C.3a viruses. The HA gene sequences of viruses in both clades 3C.2a and 3C.3a continue to diverge. Notably, clade 3C.3a.1 viruses had evolved to carry HA1 amino acid substitutions of L3I, S91N, N144K (loss of a N-linked glycosylation motif at residues 144-146), F193S and K326R, and D160N in HA2, compared with cell culture-propagated A/Stockholm/6/2014. Greater variation has been observed among clade 3C.2a viruses, resulting in the designation of new subclades/groups/subgroups. Amino acid substitutions that define these subclades/groups/subgroups are: • Subclade 3C.2a1: Those in clade 3C.2a plus N171K in HA1 and I77V and G155E in HA2, most also carry N121K in HA1, e.g. A/Singapore/INFIMH-16-0019/2016 (a former vaccine virus). • Group 3C.2a1a: Those in subclade 3C.2a1 plus T135K in HA1, resulting in the loss of a potential glycosylation site, and G150E in HA2, e.g. A/Greece/4/2017. • Group 3C.2a1b: Those in subclade 3C.2a1 plus E62G, R142G and H311Q in HA1, often with additional amino acid substitutions – notably HA1 T135K (resulting in the loss of a potential glycosylation site) commonly with T128A (resulting in the loss of a potential glycosylation site), the 3C.2a1b.1 subgroup (e.g. A/La Rioja/2202/2018) or HA1 T131K and HA2 V200I, the 3C.2a1b.2 subgroup (e.g. A/South Australia/34/2019). Distinct clusters of viruses within both these subgroups have emerged defined by specific HA1 and/or HA2 amino acid substitutions: 3C.2a1b.1a with additional amino acid substitutions of HA1 A138S, F193S and S198P, many also with G186D and D190N (e.g. A/Denmark/3284/2019); 3C.2a1b.1b with additional amino acid substitutions of HA1 S137F, A138S and F193S (e.g. A/Hong Kong/2671/2019); 3C.2a1b.2a with additional amino acid substitutions of HA1 K83E and Y94N with HA2 I193M (e.g. A/Slovenia/1637/2020); 3C.2a1b.2b with HA2 V18M substitution, often with additional HA1 substitutions (e.g. A/Bretagne/1323/2020). • Clade 3C.3a: represented by a former vaccine virus, A/Switzerland/9715293/2013, with recently circulating clade 3C.3a.1 viruses carrying additional substitutions of S91N, N144K (resulting in the loss of a potential glycosylation site), and F193S in HA1 and D160N in HA2, e.g. A/England/538/2018 and A/Kansas/14/2017, the A(H3N2) vaccine virus for the 2019-2020 northern hemisphere influenza season. The significant geographic spread of viruses in the antigenically distinct 3C.2a1b.1b cluster, influenced the selection of an A/Hong Kong/2671/2019-like or an A/Hong Kong/45/2019-like virus as the A(H3N2) component of vaccines for the 2020-2021 northern hemisphere and 2021 southern hemisphere influenza seasons. The first phylogeny was based on a representative set of HA sequences derived from viruses with collection dates after 30 April 2022 made available in GISAID and generated at the WIC from 01 July 2022 (Figure 3a). Small numbers of ʻCambodia-likeʼ 3C.2a1b.2a.1 (from China) and 3C.2a1b.1a (from Denmark, Germany and Sweden) viruses were reported on. The vast majority of recently collected viruses were ʻBangladesh-likeʼ (3C.2a1b.2a.2 with HA1 substitutions of Y159N, T160I (loss of a glycosylation site), L164Q, G186D, D190N and Y195F). The latter viruses were split into four major subgroups defined by specific HA1 amino acid substitutions: (i) E50K; (ii) D53N and P289S; (iii) D53N, N96S (gain a glycosylation site) and I192F; (iv) D53G often with I25V, R201K and S219Y or D104G and K276R. Subgroups (ii), (iii) and (iv) also share HA1 H156S amino acid substitution. Sequences derived from samples collected in the WHO European Region were dispersed throughout the trees with the ʻBangladesh-likeʼ (3C.2a1b.2a.2) viruses falling into multiple virus clusters defined by specific amino acid substitutions (Figure 3a). The second phylogeny is based on HA sequences derived from viruses with collection dates after 31 July 2022 made available in GISAID and generated at the WIC from 01 August 2022 and shows a very similar profile to the first phylogeny (Table 2 and Figure 3b). With the caveat that a large number of sequences from viruses with collection dates in August and September 2022, detected in Spain, are now available in GISAID, subgroups (i; HA1 substitution E50K) and (iv; HA1 substitutions of D53G, D104G and K276R) dominate in both phylogenies and there is expansion subgroup (iv) with additional HA1 I140K and R299K substitutions. The locations of HA sequences for egg- and cell culture-propagated cultivars of A/Cambodia/e0826360/2020 (3C.2a1b.2a.1) recommended for use in northern hemisphere 2021-2022 vaccines [1], are indicated in red on the phylogenies, as are egg- and cell-culture based ʻBangladesh-likeʼ vaccines to be used in the 2022 and 2023 southern hemisphere and 2022-2023 northern hemisphere seasons, A/Darwin/9/2021 and A/Darwin/6/2021 (3C.2a1b.2a.2) respectively [2, 4, 3] (Figures 3a and 3b). WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 16 As described in many previous reports2, influenza A(H3N2) viruses had been difficult to characterise antigenically by HI assay due to variable agglutination of red blood cells (RBCs) from guinea pigs, turkeys, and humans, often with the loss of ability to agglutinate any of these RBCs. As was highlighted first in the November 2014 report3, this was a significant problem for most viruses that fell in genetic clade 3C.2a, although there was some alleviation of this during 2019-2020 with continuation into the 2020-2021 influenza season. This issue is now much alleviated for ʻBangladesh-likeʼ 3C.2a1b.2a.2 viruses which agglutinate guinea pig RBCs well, allowing HI assays to be performed with single A(H3N2) viruses from Croatia and the Netherlands failing to yield a sufficient HA titre with guinea pig RBCs to allow HI analysis (Table 3). While the number of detections of seasonal influenza viruses was low from April 2020 to July 2021, compared to previous years, the WHO Collaborating Centres for Influenza have shown viruses in these emerged virus clusters to be antigenically distinguishable from one another and other A(H3N2) virus subgroups. Results for 97 A(H3N2) viruses fully characterised antigenically since the July report are shown in Tables 5-1 to 5-5. Of the test viruses, three fell in the 3C.2a1b.1a cluster, one in the 3C.2a1b.1b cluster, 92 were ʻBangladesh-likeʼ 3C.2a1b.2a.2 viruses and the one virus for which gene sequencing is pending gave an HI profile indicative of a 3C.2a1b.2a.2 virus. The two 3C.2a1b.1a viruses detected in France were recognised well, within fourfold of the respective homologous titres, by antisera raised against five reference viruses inclusive of that raised against the northern hemisphere 2022-2023 vaccine virus, A/Darwin9/2021 (Table 5-3). The 3C.2a1b.1b virus was recognised well by antisera raised against cell culture-propagated A/Denmark/3264/2019 (3C.2a1b.1a), A/Hong Kong/2671/2019 (3C.2a1b.1b) and A/Cambodia/925256/2020 (3C.2a1b.2a.1) (Table 5-4). Viruses with 3C.2a1b.2a.2 HAs are arranged by genetic cluster H156 (i; HA1 substitution E50K), H156S (iii; HA1 substitutions D53N, H156S), D53G (iv; HA1 substitutions D53G, H156S) and D104G (iv; HA1 substitutions D53G, D104G, H156S, K276R) (Tables 5-1 to 5-5). These ʻBangladesh-likeʼ 3C.2a1b.2a.2 test viruses were recognised well only by post-infection ferret antisera raised against viruses with 3C.2a1b.2a.2 HAs, and only the H156S substitution resulted in slight loss of reactivity. Overall, antisera raised against cell culture-propagated A/Bangladesh/4005/2020, A/Stockholm/5/2021 and A/England/214191723/2021 all recognised greater than 97% of the test viruses at titres within fourfold of the respective homologous titres. Although only small numbers of test viruses were analysed for antisera raised against cell culture-propagated A/Slovenia/8720/2022 and A/Thuringen10/2022, and egg-propagated A/Slovenia/8720/2022, at least 95% were recognised at titres within fourfold of the respective homologous titres. The antiserum raised against egg-propagated A/Darwin/9/2021, the northern hemisphere 2022-2023 vaccine virus, recognised 84 (90%) of the test viruses at titres within fourfold of the homologous titres. Results of HI assays with panels of post-infection ferret antisera raised against A(H3N2) vaccine and reference viruses for viruses detected in EU/EEA countries can be seen in previous influenza characterisation reports on ECDCʼs website. Overall, these data show strong clade/subclade-specific recognition of test viruses by post-infection ferret antisera raised against cell culture-propagated reference viruses, with limited cross-clade/subclade recognition and further reductions in recognition of cell culture-propagated recently circulating viruses by antisera raised against A(H3N2) egg-propagated vaccine viruses. _____ 2 For example, the September 2013 report: European Centre for Disease Prevention and Control. Influenza virus characterisation, summary Europe, September 2013. Stockholm: ECDC; 2013. Available from: https://ecdc.europa.eu/sites/portal/files/media/en/publications/Publications/influenza-virus-characterisation-sep-2013.pdf 3 European Centre for Disease Prevention and Control. Influenza virus characterisation, summary Europe, November 2014. Stockholm: ECDC; 2014. Available from: https://www.ecdc.europa.eu/sites/default/files/media/en/publications/Publications/ERLI-Net%20report%20November%202014.pdf WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 17 Figure 3a. Phylogenetic comparison of influenza A(H3N2) HA genes (GISAID/WIC, July 2022) WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 18 Figure 3b. Phylogenetic comparison of influenza A(H3N2) HA genes (GISAID/WIC, Sept 2022) WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 19 Table 5-1. Antigenic analysis of influenza A(H3N2) viruses by HI Vi ru se s O th er C ol le ct io n Pa ss ag e A/ D en m ar k A/ H K A/ C am b A/ C am b A/ B an g A/ St oc k A/ En g A/ D ar w in A/ K an sa s in fo rm at io n da te hi st or y 32 64 /1 9 26 71 /1 9 92 52 56 /2 0 e0 82 63 60 /2 0 40 05 /2 0 5/ 21 21 41 91 72 3/ 21 9/ 21 14 /1 7 Pa ss ag e hi st or y SI AT C el l SI AT Eg g SI AT SI AT SI AT Eg g SI AT Fe rr et n um be r F1 9/ 20 *1 St J ud es F2 1/ 20 *1 F0 3/ 21 *1 F1 0/ 21 *1 F0 7/ 21 *1 F3 5/ 21 *1 F0 7/ 22 *1 F3 9/ 21 *1 F1 7/ 19 *1 G en et ic g ro up 3C .2 a1 b. 1a 3C .2 a1 b. 1b 3C .2 a1 b. 2a .1 3C .2 a1 b. 2a .1 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .3 a. 1 R EF ER EN C E VI R U SE S A/ D en m ar k/ 32 64 /2 01 9 3C .2 a1 b. 1a 20 19 -1 0- 25 SI AT 3/ SI AT 4 32 0 16 0 64 0 32 0 32 0 16 0 40 32 0 16 0 A/ H on g K on g/ 26 71 /2 01 9 3C .2 a1 b. 1b 20 19 -0 6- 17 M D C K 1/ SI AT 4 32 0 32 0 64 0 16 0 32 0 80 40 16 0 16 0 A/ C am bo di a/ 92 52 56 /2 02 0 3C .2 a1 b. 2a .1 20 20 -0 9- 25 SI AT 5 16 0 16 0 32 0 32 0 32 0 16 0 40 32 0 16 0 A/ C am bo di a/ e0 82 63 60 /2 02 0 3C .2 a1 b. 2a .1 20 20 -0 7- 16 E5 /E 2 16 0 < 80 12 80 32 0 16 0 16 0 16 0 80 A/ B an gl ad es h/ 40 05 /2 02 0 H 15 6 3C .2 a1 b. 2a .2 20 20 -1 0- 04 SI AT 3 16 0 40 16 0 32 0 64 0 64 0 64 0 64 0 16 0 A/ St oc kh ol m /5 /2 02 1 H 15 6S 3C .2 a1 b. 2a .2 20 21 -0 4- 16 SI AT 0/ SI AT 3 80 < 80 16 0 32 0 64 0 32 0 64 0 80 A/ En gl an d/ 21 41 91 72 3/ 20 21 H 15 6S 3C .2 a1 b. 2a .2 20 21 -1 0- 12 M D C K 1/ SI AT 2 40 < 80 16 0 16 0 32 0 64 0 64 0 40 A/ D ar w in /9 /2 02 1 H 15 6S 3C .2 a1 b. 2a .2 20 21 -0 4- 17 E3 /E 4 16 0 < 80 64 0 64 0 12 80 64 0 25 60 16 0 A/ K an sa s/ 14 /2 01 7 3C .3 a. 1 20 17 -1 2- 14 SI AT 3/ SI AT 2 40 < 80 80 80 80 80 80 32 0 TE ST V IR U SE S A/ Po rt ug al /2 10 27 3/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 2- 21 SI AT 1/ SI AT 2 40 < 40 40 16 0 32 0 32 0 32 0 < A/ Po rt ug al /2 10 27 4/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 2- 21 SI AT 2/ SI AT 2 80 < 40 80 32 0 64 0 32 0 64 0 < A/ Po rt ug al /2 10 37 2/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 3- 08 SI AT 2/ SI AT 2 80 < 40 80 16 0 64 0 32 0 64 0 < A/ Po rt ug al /2 10 58 8/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 3- 09 SI AT 2/ SI AT 2 40 < 40 80 16 0 64 0 32 0 64 0 < A/ Po rt ug al /2 10 59 2/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 3- 15 SI AT 1/ SI AT 2 80 < 40 80 16 0 64 0 32 0 64 0 < A/ Po rt ug al /2 10 60 3/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 3- 15 SI AT 2/ SI AT 2 80 < 40 80 16 0 64 0 32 0 32 0 < A/ Po rt ug al /2 10 61 1/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 3- 15 SI AT 2/ SI AT 2 80 < 40 80 16 0 64 0 32 0 32 0 < A/ Ire la nd /1 63 47 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 3- 21 SI AT 2 80 < 40 80 16 0 64 0 32 0 64 0 < A/ Ire la nd /2 43 47 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 4- 27 SI AT 2 80 < 40 80 32 0 64 0 32 0 64 0 < A/ C as til la L a M an ch a/ 22 34 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 5- 03 SI AT 1 80 < 40 80 16 0 64 0 32 0 64 0 < A/ C as til la L a M an ch a/ 22 24 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 5- 08 SI AT 1 80 < 40 80 16 0 32 0 32 0 32 0 < A/ C as til la L a M an ch a/ 23 33 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 5- 16 SI AT 1 40 < 40 40 16 0 32 0 32 0 32 0 < A/ C as til la L a M an ch a/ 23 58 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 5- 17 SI AT 1 40 < 40 40 16 0 32 0 32 0 32 0 < A/ C as til la L a M an ch a/ 23 56 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 5- 19 SI AT 1 80 < 40 40 16 0 32 0 32 0 32 0 < A/ Po rt ug al /2 10 26 9/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 21 SI AT 1/ SI AT 2 80 < 80 16 0 32 0 64 0 12 80 64 0 < A/ Po rt ug al /2 10 30 7/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 25 SI AT 2/ SI AT 2 80 < 40 80 32 0 32 0 64 0 64 0 < A/ Po rt ug al /2 10 31 2/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 26 SI AT 2/ SI AT 2 80 < 80 80 32 0 64 0 12 80 64 0 < A/ Po rt ug al /2 10 36 6/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 3- 04 SI AT 2/ SI AT 2 40 < 40 80 16 0 32 0 64 0 32 0 < *S up er sc rip ts re fe r t o an tis er um p ro pe rt ie s (< re la te s to th e lo w es t d ilu tio n of a nt is er um u se d) Va cc in e Va cc in e 1 < = <4 0, N D = N ot D on e N H 2 02 1- 22 SH 2 02 2 N H 2 02 2- 23 SH 2 02 3 H ae m ag gl ut in at io n in hi bi tio n tit re Po st -in fe ct io n fe rr et a nt is er a WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 20 Table 5-2. Antigenic analysis of influenza A(H3N2) viruses by HI Vi ru se s O th er C ol le ct io n Pa ss ag e A/ D en m ar k A/ H K A/ C am b A/ C am b A/ B an g A/ St oc k A/ En g A/ D ar w in A/ K an sa s in fo rm at io n da te hi st or y 32 64 /1 9 26 71 /1 9 92 52 56 /2 0 e0 82 63 60 /2 0 40 05 /2 0 5/ 21 21 41 91 72 3/ 21 9/ 21 14 /1 7 Pa ss ag e hi st or y SI AT C el l SI AT Eg g SI AT SI AT SI AT Eg g SI AT Fe rr et n um be r F1 9/ 20 *1 St J ud es F2 1/ 20 *1 F0 3/ 21 *1 F1 0/ 21 *1 F0 7/ 21 *1 F3 5/ 21 *1 F0 7/ 22 *1 F3 9/ 21 *1 F1 7/ 19 *1 G en et ic g ro up 3C .2 a1 b. 1a 3C .2 a1 b. 1b 3C .2 a1 b. 2a .1 3C .2 a1 b. 2a .1 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .3 a. 1 R EF ER EN C E VI R U SE S A/ D en m ar k/ 32 64 /2 01 9 3C .2 a1 b. 1a 20 19 -1 0- 25 SI AT 3/ SI AT 4 64 0 16 0 64 0 32 0 32 0 16 0 40 32 0 16 0 A/ H on g K on g/ 26 71 /2 01 9 3C .2 a1 b. 1b 20 19 -0 6- 17 M D C K 1/ SI AT 4 32 0 64 0 64 0 16 0 32 0 80 40 16 0 16 0 A/ C am bo di a/ 92 52 56 /2 02 0 3C .2 a1 b. 2a .1 20 20 -0 9- 25 SI AT 5 16 0 16 0 64 0 32 0 32 0 16 0 40 32 0 16 0 A/ C am bo di a/ e0 82 63 60 /2 02 0 3C .2 a1 b. 2a .1 20 20 -0 7- 16 E5 /E 2 16 0 < 80 12 80 32 0 16 0 16 0 16 0 80 A/ B an gl ad es h/ 40 05 /2 02 0 H 15 6 3C .2 a1 b. 2a .2 20 20 -1 0- 04 SI AT 3 16 0 40 16 0 32 0 64 0 64 0 64 0 64 0 16 0 A/ St oc kh ol m /5 /2 02 1 H 15 6S 3C .2 a1 b. 2a .2 20 21 -0 4- 16 SI AT 0/ SI AT 3 80 < 80 16 0 32 0 32 0 32 0 64 0 80 A/ En gl an d/ 21 41 91 72 3/ 20 21 H 15 6S 3C .2 a1 b. 2a .2 20 21 -1 0- 12 M D C K 1/ SI AT 2 40 < 80 16 0 16 0 32 0 64 0 64 0 40 A/ D ar w in /9 /2 02 1 H 15 6S 3C .2 a1 b. 2a .2 20 21 -0 4- 17 E3 /E 4 16 0 < 80 64 0 64 0 12 80 64 0 12 80 16 0 A/ K an sa s/ 14 /2 01 7 3C .3 a. 1 20 17 -1 2- 14 SI AT 3/ SI AT 2 40 < 80 80 80 80 80 80 16 0 TE ST V IR U SE S A/ D un ke rq ue /5 19 79 /2 02 1 D 10 4G 3C .2 a1 b. 2a .2 20 21 -1 2- 24 SI AT 1 40 < 40 40 16 0 32 0 32 0 32 0 40 A/ Po rt ug al /2 10 25 9/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 2- 17 SI AT 1/ SI AT 2 80 < 80 80 16 0 64 0 32 0 64 0 40 A/ N or d Pa s de C al ai s/ 11 65 9/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 2- 17 SI AT 1 80 < 80 80 16 0 32 0 32 0 32 0 40 A/ Po rt ug al /2 10 26 6/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 2- 18 SI AT 1/ SI AT 2 40 < 40 40 16 0 32 0 32 0 32 0 40 A/ D un ke rq ue /1 69 08 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 3- 01 SI AT 1 80 < 40 16 0 16 0 32 0 32 0 32 0 40 A/ Po rt ug al /2 10 59 7/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 3- 09 SI AT 1/ SI AT 2 80 < 40 40 16 0 64 0 32 0 64 0 40 A/ M on te ne gr o/ 15 57 21 22 02 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 3- 09 SI AT 1 80 < 80 80 16 0 32 0 32 0 64 0 40 A/ M on te ne gr o/ 16 14 82 22 02 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 3- 17 SI AT 1 40 < 40 40 16 0 32 0 32 0 32 0 40 A/ M on te ne gr o/ 16 51 63 22 02 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 3- 23 SI AT 1 40 < 40 40 16 0 32 0 32 0 32 0 40 A/ M on te ne gr o/ 16 51 69 22 02 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 3- 23 SI AT 1 80 < 16 0 16 0 32 0 64 0 64 0 64 0 80 A/ Pa ys d e Lo ire /2 23 33 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 3- 24 SI AT 1 80 < 40 80 16 0 64 0 32 0 64 0 40 A/ M on te ne gr o/ 17 14 47 22 02 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 4- 01 SI AT 1 80 < 40 80 16 0 32 0 32 0 64 0 40 A/ G ar ch es /2 83 67 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 4- 06 SI AT 1 80 < 40 80 16 0 32 0 32 0 32 0 40 A/ Al sa ce /2 85 44 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 4- 08 SI AT 1 80 < 80 80 16 0 64 0 32 0 64 0 40 A/ Pi ca rd ie /2 93 31 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 4- 13 SI AT 1 40 < 40 40 80 32 0 32 0 32 0 40 A/ Sa ra je vo /1 92 G /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 4- 19 SI AT 2/ SI AT 2 80 < 40 80 16 0 32 0 32 0 64 0 40 A/ Sa in t-D en is /4 84 07 /2 02 1 H 15 6S 3C .2 a1 b. 2a .2 20 21 -1 2- 06 SI AT 1 < < 80 80 80 16 0 32 0 32 0 < A/ Po rt ug al /2 10 19 2/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 08 SI AT 2/ SI AT 2 80 < 40 80 16 0 32 0 64 0 32 0 40 A/ Po rt ug al /2 10 21 0/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 09 SI AT 2/ SI AT 2 80 < 80 16 0 16 0 32 0 64 0 32 0 40 A/ Po rt ug al /2 10 21 4/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 10 SI AT 1/ SI AT 2 80 < 80 16 0 32 0 32 0 64 0 64 0 40 A/ Po rt ug al /2 10 21 2/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 11 SI AT 2/ SI AT 2 80 < 80 16 0 32 0 64 0 12 80 64 0 40 A/ Po rt ug al /2 10 22 0/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 11 SI AT 1/ SI AT 2 80 < 80 16 0 32 0 64 0 12 80 64 0 40 A/ Po rt ug al /2 10 21 8/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 14 SI AT 1/ SI AT 2 80 < 80 80 32 0 32 0 64 0 64 0 40 A/ Po rt ug al /2 10 21 9/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 14 SI AT 2/ SI AT 2 80 < 40 40 16 0 32 0 64 0 32 0 40 A/ Po rt ug al /2 10 22 4/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 14 SI AT 2/ SI AT 2 80 < 40 80 32 0 32 0 64 0 64 0 40 A/ Po rt ug al /2 10 25 5/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 16 SI AT 1/ SI AT 2 80 < 80 16 0 32 0 64 0 12 80 64 0 40 A/ Po rt ug al /2 10 25 6/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 16 SI AT 2/ SI AT 2 80 < 80 80 32 0 64 0 64 0 64 0 40 A/ Po rt ug al /2 10 25 7/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 16 SI AT 2/ SI AT 2 80 < 80 16 0 32 0 64 0 12 80 64 0 80 A/ Po rt ug al /2 10 25 8/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 16 SI AT 2/ SI AT 2 80 < 80 80 32 0 64 0 12 80 64 0 40 A/ Po rt ug al /2 10 27 0/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 21 SI AT 1/ SI AT 2 80 < 80 16 0 32 0 64 0 12 80 64 0 40 A/ Po rt ug al /2 10 27 1/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 22 SI AT 1/ SI AT 2 80 < 80 80 16 0 32 0 64 0 64 0 40 A/ Le M an s/ 16 90 7/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 3- 02 SI AT 1 40 < 40 80 16 0 32 0 64 0 32 0 40 A/ M ou lin s/ R 22 .3 21 .9 8/ 20 22 H 15 6 3C .2 a1 b. 2a .2 20 22 -0 7- 20 M D C K x/ SI AT 1 16 0 < 80 32 0 64 0 32 0 32 0 32 0 80 A/ M ou lin s/ R 22 .3 21 .9 6/ 20 22 H 15 6 3C .2 a1 b. 2a .2 20 22 -0 7- 20 M D C K x/ SI AT 1 16 0 < 80 16 0 32 0 32 0 32 0 32 0 80 A/ Ly on /C H U /R 22 .3 20 .8 5/ 20 22 H 15 6 3C .2 a1 b. 2a .2 20 22 -0 7- 24 M D C K x/ SI AT 1 80 < 40 80 32 0 32 0 32 0 16 0 80 *S up er sc rip ts re fe r t o an tis er um p ro pe rt ie s (< re la te s to th e lo w es t d ilu tio n of a nt is er um u se d) Va cc in e Va cc in e 1 < = <4 0, N D = N ot D on e N H 2 02 1- 22 SH 2 02 2 N H 2 02 2- 23 SH 2 02 3 H ae m ag gl ut in at io n in hi bi tio n tit re Po st -in fe ct io n fe rr et a nt is er a WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 21 Table 5-3. Antigenic analysis of influenza A(H3N2) viruses by HI N EW N EW Vi ru se s O th er C ol le ct io n Pa ss ag e A/ D en m ar k A/ H K A/ C am b A/ C am b A/ B an g A/ B an g A/ St oc k A/ En g A/ En g A/ Sl ov A/ D ar w in A/ Sl o A/ K an sa s in fo rm at io n da te hi st or y 32 64 /1 9 26 71 /1 9 92 52 56 /2 0 e0 82 63 60 /2 0 40 05 /2 0 40 05 /2 0 5/ 21 21 41 91 72 3/ 21 21 41 91 72 3/ 21 87 20 /2 02 2 9/ 21 87 20 /2 2 14 /1 7 Pa ss ag e hi st or y SI AT C el l SI AT Eg g SI AT SI AT SI AT SI AT SI AT SI AT Eg g Eg g SI AT Fe rr et n um be r F1 9/ 20 *1 St J ud es F2 1/ 20 *1 F0 3/ 21 *1 F1 0/ 21 *1 F0 7/ 21 *1 F3 1/ 22 *1 F3 5/ 21 *1 F0 7/ 22 *1 F3 2/ 22 *1 F2 4/ 22 *1 F3 9/ 21 *1 F2 5/ 22 *1 F1 7/ 19 *1 G en et ic g ro up 3C .2 a1 b. 1a 3C .2 a1 b. 1b 3C .2 a1 b. 2a .1 3C .2 a1 b. 2a .1 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .3 a. 1 R EF ER EN C E VI R U SE S A/ D en m ar k/ 32 64 /2 01 9 3C .2 a1 b. 1a 20 19 -1 0- 25 SI AT 3/ SI AT 4 32 0 16 0 64 0 32 0 32 0 32 0 16 0 40 < N D 32 0 40 16 0 A/ H on g K on g/ 26 71 /2 01 9 3C .2 a1 b. 1b 20 19 -0 6- 17 M D C K 1/ SI AT 4 32 0 32 0 64 0 16 0 32 0 32 0 80 40 40 < 16 0 40 16 0 A/ C am bo di a/ 92 52 56 /2 02 0 3C .2 a1 b. 2a .1 20 20 -0 9- 25 SI AT 5 16 0 16 0 12 80 32 0 32 0 64 0 16 0 40 < N D 32 0 40 16 0 A/ C am bo di a/ e0 82 63 60 /2 02 0 3C .2 a1 b. 2a .1 20 20 -0 7- 16 E5 /E 2 16 0 < 80 25 60 32 0 64 0 16 0 16 0 16 0 32 0 16 0 80 80 A/ B an gl ad es h/ 40 05 /2 02 0 H 15 6 3C .2 a1 b. 2a .2 20 20 -1 0- 04 SI AT 3 16 0 40 16 0 32 0 64 0 64 0 64 0 64 0 16 0 12 80 64 0 32 0 16 0 A/ St oc kh ol m /5 /2 02 1 H 15 6S 3C .2 a1 b. 2a .2 20 21 -0 4- 16 SI AT 0/ SI AT 3 80 < 80 16 0 32 0 16 0 64 0 32 0 16 0 12 80 64 0 32 0 80 A/ En gl an d/ 21 41 91 72 3/ 20 21 H 15 6S 3C .2 a1 b. 2a .2 20 21 -1 0- 12 M D C K 1/ SI AT 2 40 < 80 16 0 16 0 16 0 32 0 64 0 32 0 12 80 64 0 32 0 40 A/ Sl ov en ia /8 72 0/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 2- 10 SI AT 1/ M D C K 1/ SI AT 2 16 0 < 16 0 80 32 0 N D 12 80 12 80 N D 32 0 64 0 N D 40 A/ D ar w in /9 /2 02 1 H 15 6S 3C .2 a1 b. 2a .2 20 21 -0 4- 17 E3 /E 2 16 0 < 80 64 0 64 0 32 0 12 80 64 0 32 0 64 0 64 0 12 80 16 0 A/ Sl ov en ia /8 72 0/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 2- 10 E3 (A m 1A l2 ) 16 0 < 80 32 0 32 0 N D 64 0 64 0 N D 32 0 64 0 64 0 80 A/ K an sa s/ 14 /2 01 7 3C .3 a. 1 20 17 -1 2- 14 SI AT 3/ SI AT 2 40 < 80 80 80 80 80 80 < 80 80 < 64 0 TE ST V IR U SE S A/ C ro at ia /6 62 13 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 3- 23 SI AT 1 80 < 40 80 16 0 N D 32 0 32 0 N D 16 0 32 0 32 0 80 A/ C ro at ia /7 07 23 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 4- 06 SI AT 1 80 < 40 80 16 0 N D 64 0 64 0 N D 64 0 64 0 12 80 < A/ C ro at ia /7 07 08 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 4- 06 SI AT 1 40 < 40 40 16 0 N D 64 0 32 0 N D 32 0 64 0 64 0 < A/ C ro at ia /7 06 97 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 4- 06 SI AT 2 80 < 40 40 16 0 N D 64 0 32 0 N D 32 0 32 0 64 0 < A/ C ro at ia /7 06 54 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 4- 06 SI AT 2 < < < < 80 N D 80 16 0 N D 40 16 0 16 0 < A/ C ro at ia /7 06 48 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 4- 06 SI AT 2 40 < 40 < 16 0 N D 16 0 16 0 N D 32 0 16 0 64 0 < A/ C ro at ia /7 06 45 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 4- 06 SI AT 2 80 < 40 80 16 0 N D 16 0 32 0 N D 16 0 32 0 32 0 < A/ Sa ra je vo /1 86 G /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 4- 09 SI AT 1 80 < 40 80 16 0 N D 64 0 32 0 N D 32 0 64 0 64 0 < A/ Sa ra je vo /1 89 G /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 4- 18 SI AT 1 40 < 40 40 16 0 N D 32 0 32 0 N D 32 0 32 0 32 0 < A/ C ro at ia /7 73 72 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 5- 07 SI AT 1 80 < 40 40 16 0 N D 64 0 32 0 N D 32 0 32 0 64 0 < A/ C ro at ia /7 94 86 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 5- 17 SI AT 1 80 80 80 80 16 0 N D 32 0 32 0 N D 32 0 32 0 64 0 < A/ Po rt ug al /2 10 20 9/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 09 SI AT 1/ SI AT 3 40 < 40 40 16 0 N D 32 0 64 0 N D 80 32 0 32 0 40 A/ Po rt ug al /2 10 20 7/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 2- 10 SI AT 2/ SI AT 3 40 < 40 80 16 0 N D 32 0 12 80 N D 32 0 32 0 64 0 40 A/ Ile d e Fr an ce /0 84 40 /2 02 2 3C .2 a1 b. 1a 20 22 -0 2- 01 SI AT 3 80 80 32 0 16 0 80 N D 16 0 40 N D < 16 0 40 80 A/ Pa ys d e Lo ire /1 35 61 /2 02 2 3C .2 a1 b. 1a 20 22 -0 2- 24 SI AT 2 80 80 32 0 16 0 80 N D 16 0 < N D < 16 0 < 80 *S up er sc rip ts re fe r t o an tis er um p ro pe rt ie s (< re la te s to th e lo w es t d ilu tio n of a nt is er um u se d) Va cc in e Va cc in e 1 < = <4 0, N D = N ot D on e N H 2 02 1- 22 SH 2 02 2 N H 2 02 2- 23 SH 2 02 3 H ae m ag gl ut in at io n in hi bi tio n tit re Po st -in fe ct io n fe rr et a nt is er a WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 22 Table 5-4. Antigenic analysis of influenza A(H3N2) viruses by HI Vi ru se s O th er C ol le ct io n Pa ss ag e A/ D en m ar k A/ H K A/ C am b A/ C am b A/ B an g A/ St oc k A/ En g A/ Sl ov A/ D ar w in A/ Sl o A/ K an sa s in fo rm at io n da te hi st or y 32 64 /1 9 26 71 /1 9 92 52 56 /2 0 e0 82 63 60 /2 0 40 05 /2 0 5/ 21 21 41 91 72 3/ 21 87 20 /2 02 2 9/ 21 87 20 /2 2 14 /1 7 Pa ss ag e hi st or y SI AT C el l SI AT Eg g SI AT SI AT SI AT SI AT Eg g Eg g SI AT Fe rr et n um be r F1 9/ 20 *1 St J ud es F2 1/ 20 *1 F0 3/ 21 *1 F1 0/ 21 *1 F0 7/ 21 *1 F3 5/ 21 *1 F0 7/ 22 *1 F2 4/ 22 *1 F3 9/ 21 *1 F2 5/ 22 *1 F1 7/ 19 *1 G en et ic g ro up 3C .2 a1 b. 1a 3C .2 a1 b. 1b 3C .2 a1 b. 2a .1 3C .2 a1 b. 2a .1 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .3 a. 1 R EF ER EN C E VI R U SE S A/ D en m ar k/ 32 64 /2 01 9 3C .2 a1 b. 1a 20 19 -1 0- 25 SI AT 3/ SI AT 4 32 0 32 0 64 0 32 0 32 0 16 0 40 N D 32 0 40 16 0 A/ H on g K on g/ 26 71 /2 01 9 3C .2 a1 b. 1b 20 19 -0 6- 17 M D C K 1/ SI AT 4 32 0 32 0 64 0 16 0 32 0 16 0 80 < 16 0 40 16 0 A/ C am bo di a/ 92 52 56 /2 02 0 3C .2 a1 b. 2a .1 20 20 -0 9- 25 SI AT 5 16 0 16 0 12 80 32 0 32 0 16 0 80 N D 64 0 40 16 0 A/ C am bo di a/ e0 82 63 60 /2 02 0 3C .2 a1 b. 2a .1 20 20 -0 7- 16 E5 /E 2 16 0 < 16 0 12 80 32 0 16 0 32 0 32 0 32 0 16 0 80 A/ B an gl ad es h/ 40 05 /2 02 0 H 15 6 3C .2 a1 b. 2a .2 20 20 -1 0- 04 SI AT 3 16 0 40 32 0 32 0 64 0 64 0 64 0 12 80 64 0 32 0 16 0 A/ St oc kh ol m /5 /2 02 1 H 15 6S 3C .2 a1 b. 2a .2 20 21 -0 4- 16 SI AT 0/ SI AT 3 80 < 80 16 0 32 0 64 0 32 0 12 80 64 0 32 0 40 A/ En gl an d/ 21 41 91 72 3/ 20 21 H 15 6S 3C .2 a1 b. 2a .2 20 21 -1 0- 12 M D C K 1/ SI AT 3 40 < 80 16 0 16 0 32 0 64 0 12 80 64 0 32 0 < A/ Sl ov en ia /8 72 0/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 2- 10 SI AT 1/ M D C K 1/ SI AT 2 80 < 80 80 16 0 64 0 64 0 64 0 64 0 12 80 < A/ D ar w in /9 /2 02 1 H 15 6S 3C .2 a1 b. 2a .2 20 21 -0 4- 17 E3 /E 2 16 0 < 80 64 0 32 0 64 0 64 0 64 0 12 80 12 80 80 A/ Sl ov en ia /8 72 0/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 2- 10 E3 (A m 1A l2 ) 16 0 < 80 32 0 32 0 64 0 64 0 32 0 64 0 12 80 40 A/ K an sa s/ 14 /2 01 7 3C .3 a. 1 20 17 -1 2- 14 SI AT 3/ SI AT 2 40 40 80 80 80 16 0 80 80 32 0 < 64 0 TE ST V IR U SE S A/ B el gi um /S 04 46 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 2- 21 SI AT 1/ SI AT 1 40 < 40 80 16 0 32 0 32 0 N D 32 0 64 0 < A/ B re st /9 32 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 3- 28 M D C K x/ SI AT 1 40 < 40 80 16 0 32 0 32 0 N D 32 0 64 0 < A/ To ul on /7 60 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 3- 28 M D C K x/ SI AT 1 80 < 80 16 0 32 0 32 0 32 0 N D 32 0 12 80 < A/ Ly on /8 08 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 4- 15 M D C K x/ SI AT 1 80 < 40 80 16 0 32 0 32 0 N D 32 0 64 0 < A/ Ly on /8 54 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 5- 04 M D C K x/ SI AT 1 40 < 40 80 16 0 32 0 32 0 N D 32 0 64 0 < A/ Ly on /C H U -R 22 .2 42 .8 2/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 5- 09 M D C K x/ SI AT 1 40 < 40 80 16 0 32 0 32 0 N D 32 0 64 0 < A/ N or w ay /2 54 83 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 6- 13 SI AT 1 80 < 40 80 16 0 32 0 32 0 N D 64 0 12 80 < A/ Ly on /C H U -R 22 .2 85 .9 2/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 6- 26 M D C K x/ SI AT 1 80 < 40 80 32 0 32 0 32 0 64 0 64 0 64 0 < A/ N or w ay /2 69 59 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 6- 29 SI AT 1 80 < 40 80 32 0 64 0 64 0 N D 64 0 12 80 < A/ N or w ay /2 79 42 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 7- 09 SI AT 1 80 < 40 80 32 0 64 0 32 0 N D 64 0 64 0 < A/ N or w ay /2 74 59 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 7- 11 SI AT 1 40 < < 40 16 0 32 0 32 0 32 0 32 0 64 0 < A/ N or w ay /2 85 42 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 7- 12 SI AT 1 40 < 40 80 16 0 32 0 32 0 32 0 32 0 64 0 < A/ N or w ay /2 78 49 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 7- 13 SI AT 1 40 < < 40 16 0 16 0 16 0 32 0 32 0 64 0 < A/ B el gi um /S 08 91 /2 02 2 D 53 G 3C .2 a1 b. 2a .2 20 22 -0 3- 20 SI AT 1/ SI AT 1 16 0 < 16 0 32 0 64 0 12 80 64 0 64 0 12 80 12 80 80 A/ B el gi um /G 01 16 /2 02 2 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 3- 14 SI AT 1/ SI AT 1 40 < 80 80 16 0 64 0 64 0 N D 64 0 32 0 40 A/ Ly on /C H U -R 22 .2 64 .8 4/ 20 22 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 6- 02 M D C K x/ SI AT 1 80 < 80 16 0 32 0 32 0 64 0 16 0 64 0 32 0 40 A/ B ou rg oi ne /7 58 /2 02 2 H 15 6 3C .2 a1 b. 2a .2 20 22 -0 4- 09 M D C K x/ SI AT 1 16 0 < 16 0 32 0 64 0 32 0 32 0 N D 32 0 16 0 80 A/ Ly on /2 71 /2 02 2 3C .2 a1 b. 1b 20 22 -0 2- 07 M D C K x/ SI AT 1 32 0 32 0 64 0 < 80 80 < N D 80 < 40 *S up er sc rip ts re fe r t o an tis er um p ro pe rt ie s (< re la te s to th e lo w es t d ilu tio n of a nt is er um u se d) Va cc in e Va cc in e 1 < = <4 0, N D = N ot D on e N H 2 02 1- 22 SH 2 02 2 N H 2 02 2- 23 SH 2 02 3 H ae m ag gl ut in at io n in hi bi tio n tit re Po st -in fe ct io n fe rr et a nt is er a WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 23 Table 5-5. Antigenic analysis of influenza A(H3N2) viruses by HI N EW Vi ru se s O th er C ol le ct io n Pa ss ag e A/ D en m ar k A/ H K A/ C am b A/ C am b A/ B an g A/ St oc k A/ En g A/ Th ur in ge n A/ D ar w in A/ K an sa s in fo rm at io n da te hi st or y 32 64 /1 9 26 71 /1 9 92 52 56 /2 0 e0 82 63 60 /2 0 40 05 /2 0 5/ 21 21 41 91 72 3/ 21 10 /2 2 9/ 21 14 /1 7 Pa ss ag e hi st or y SI AT C el l SI AT Eg g SI AT SI AT SI AT SI AT Eg g SI AT Fe rr et n um be r F1 9/ 20 *1 St J ud es F2 1/ 20 *1 F0 3/ 21 *1 F1 0/ 21 *1 F0 7/ 21 *1 F3 5/ 21 *1 F0 7/ 22 *1 F3 6/ 22 *1 F3 9/ 21 *1 F1 7/ 19 *1 G en et ic g ro up 3C .2 a1 b. 1a 3C .2 a1 b. 1b 3C .2 a1 b. 2a .1 3C .2 a1 b. 2a .1 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .2 a1 b. 2a .2 3C .3 a. 1 R EF ER EN C E VI R U SE S A/ D en m ar k/ 32 64 /2 01 9 3C .2 a1 b. 1a 20 19 -1 0- 25 SI AT 3/ SI AT 5 32 0 32 0 64 0 32 0 32 0 16 0 40 N D 32 0 16 0 A/ H on g K on g/ 26 71 /2 01 9 3C .2 a1 b. 1b 20 19 -0 6- 17 M D C K 1/ SI AT 5 32 0 32 0 64 0 16 0 32 0 16 0 40 < 32 0 16 0 A/ C am bo di a/ 92 52 56 /2 02 0 3C .2 a1 b. 2a .1 20 20 -0 9- 25 SI AT 5 16 0 16 0 12 80 32 0 32 0 16 0 80 N D 64 0 16 0 A/ C am bo di a/ e0 82 63 60 /2 02 0 3C .2 a1 b. 2a .1 20 20 -0 7- 16 E5 /E 2 80 < 80 12 80 16 0 16 0 32 0 80 32 0 80 A/ B an gl ad es h/ 40 05 /2 02 0 H 15 6 3C .2 a1 b. 2a .2 20 20 -1 0- 04 SI AT 3 16 0 40 16 0 16 0 64 0 64 0 64 0 32 0 64 0 16 0 A/ St oc kh ol m /5 /2 02 1 H 15 6S 3C .2 a1 b. 2a .2 20 21 -0 4- 16 SI AT 0/ SI AT 3 80 < 80 16 0 32 0 64 0 32 0 16 0 64 0 40 A/ En gl an d/ 21 41 91 72 3/ 20 21 H 15 6S 3C .2 a1 b. 2a .2 20 21 -1 0- 12 M D C K 1/ SI AT 3 80 < 80 80 32 0 64 0 64 0 16 0 64 0 < A/ Th ur in ge n/ 10 /2 02 2 H 15 6, I1 40 K 3C .2 a1 b. 2a .2 20 22 -0 4- 01 P1 /S IA T2 80 < 16 0 16 0 32 0 64 0 64 0 32 0 32 0 < A/ D ar w in /9 /2 02 1 H 15 6S 3C .2 a1 b. 2a .2 20 21 -0 4- 17 E3 /E 2 16 0 < 80 64 0 32 0 64 0 64 0 32 0 12 80 80 A/ K an sa s/ 14 /2 01 7 3C .3 a. 1 20 17 -1 2- 14 SI AT 3/ SI AT 2 40 40 16 0 16 0 80 16 0 80 40 32 0 64 0 TE ST V IR U SE S A/ Po la nd /5 2/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 3- 30 SI AT 2 80 < 40 80 32 0 64 0 32 0 80 64 0 < A/ Po la nd /5 8/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 4- 07 SI AT 1 80 < 40 80 16 0 64 0 32 0 80 64 0 < A/ Po la nd /6 5/ 20 22 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 4- 14 SI AT 1 80 < 80 80 32 0 64 0 64 0 16 0 64 0 < A/ N or w ay /2 83 94 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 7- 20 SI AT 2 80 < 40 80 32 0 64 0 64 0 80 64 0 < A/ N or w ay /2 83 59 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 7- 24 SI AT 3 80 < 80 80 32 0 64 0 64 0 16 0 64 0 40 A/ N or w ay /2 90 40 /2 02 2 D 10 4G 3C .2 a1 b. 2a .2 20 22 -0 7- 27 SI AT 2 80 < 16 0 16 0 32 0 64 0 64 0 16 0 12 80 40 A/ B el gi um /G 00 96 /2 02 2 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 3- 07 SI AT 1/ SI AT 1 40 < 80 80 16 0 32 0 64 0 16 0 32 0 < A/ B el gi um /S 08 22 /2 02 2 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 3- 18 SI AT 1/ SI AT 1 40 < 80 16 0 16 0 32 0 64 0 16 0 32 0 40 A/ B el gi um /S 08 26 /2 02 2 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 3- 19 SI AT 1/ SI AT 1 80 < 80 16 0 32 0 32 0 64 0 16 0 64 0 40 A/ B el gi um /G 01 53 /2 02 2 H 15 6S 3C .2 a1 b. 2a .2 20 22 -0 3- 23 SI AT 1/ SI AT 1 40 < 80 16 0 32 0 32 0 64 0 16 0 64 0 40 A/ N or w ay /2 78 53 /2 02 2 pe nd in g 20 22 -0 7- 18 SI AT 2 80 < 16 0 32 0 32 0 64 0 64 0 16 0 64 0 40 *S up er sc rip ts re fe r t o an tis er um p ro pe rt ie s (< re la te s to th e lo w es t d ilu tio n of a nt is er um u se d) Va cc in e Va cc in e 1 < = <4 0, N D = N ot D on e N H 2 02 1- 22 SH 2 02 2 N H 2 02 2- 23 SH 2 02 3 H ae m ag gl ut in at io n in hi bi tio n tit re Po st -in fe ct io n fe rr et a nt is er a WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 24 Influenza B virus analyses Influenza B/Victoria-lineage All recently circulating B/Victoria-lineage viruses have fallen in genetic clade V1A, represented by B/Brisbane/60/2008, a former vaccine virus, but with additional HA1 amino acid substitutions of I117V and N129D (e.g., B/Ireland/3154/2016). Viruses retaining full-length HAs remained antigenically similar to B/Brisbane/60/2008. However, three genetic groups (described below with amino acid substitutions/deletions relative to B/Brisbane/60/2008 indicated) containing deletions of HA gene codons emerged. Viruses in these groups were/are antigenically distinct from B/Brisbane/60/2008 and each other (as noted in the September 2018 characterisation report4 and earlier ones), such that four antigenically distinguishable groups had been circulating: • A group with double deletion of HA1 residues 162 and 163 (subclade V1A.1) with amino acid substitutions of D129G and I180V, and HA2 R151K that spread worldwide and is represented by a previous vaccine virus, B/Colorado/06/2017. No detections of viruses in this group have been reported recently. • A group with triple deletion of HA1 residues 162 to 164 (subclade V1A.2) first detected in Asia, with amino acid substitutions of I180T and K209N that showed limited geographic spread, represented by B/Hong Kong/269/2017. No detections of viruses in this group have been reported recently. • A group with triple deletion of HA1 residues 162 to 164 (subclade V1A.3) first detected in Africa, with amino acid substitution K136E often with G133R that showed geographic spread and became dominant, represented by B/Washington/02/2019 the vaccine virus first recommended for use in the 2020 southern hemisphere season and thereafter up to the 2021-2022 northern hemisphere season. The phylogeny generated for the July report, was based on sequences from viruses with collection dates after 31 March 2022 that were submitted to GISAID after March 2022 (Figure 4a). All viruses were V1A.3 subclade represented by B/Washington/02/2019. Overall, the great majority of viruses fell in the V1A.3a group characterised by HA1 N150K, G184E, N197D (resulting in loss of a glycosylation site) and R279K, with this group splitting into two subgroups designated V1A.3a.1 (characterised by HA1 V220M and P241Q substitutions, detected in China) and V1A.3a.2 (characterised by HA1 A127T, P144L and K203R, often with additional substitutions, which has spread worldwide and is represented by the B/Austria/1359417/2021 vaccine virus). Sequences submitted by the Netherlands split between the V1A.3a.2 subgroup and subclade V1A.3, with the latter viruses being similar to those from Kenya having HA1 K75E, E128K, T155A and G230N substitutions, but with an additional HA1 G184R substitution sometimes with D129N (Figure 4a). The phylogeny generated for this September report contains HA sequences from viruses with collection dates after 28 February 2022 that were submitted to GISAID after July 2022 (Figure 4b). Of the sequences released for V1A.3a viruses, only two from China fall in the V1A.3a.1 subgroup, all others were from V1A.3a.2 subgroup viruses that show wide geographic spread with emergence of virus clusters defined by specific HA1 amino acid substitutions in some countries, e.g., H122Q in China, K56N in Timore-Leste and Q200P in Brazil. Sequences for viruses in subclade V1A.3 (B/Washington/02/2019-like) available since the July report were detected in Germany (n =1), China (n = 1), Netherlands (n = 8) and Spain (n = 1). Of note the virus from Spain, with a collection date in August 2022, clustered with those from the Netherlands and carried the HA1 G184R amino acid substitution; this is the first report of such a virus outside of the Netherlands. The WHO Collaborating Centres for Influenza Research and Response have shown the V.1A.3a group viruses with additional HA1 substitutions to be antigenically distinct from one another. While relatively few B/Victoria-lineage viruses have been available for detailed antigenic characterisation, those characterised earlier in the 2021-2022 season were subgroup V1A.3a.2 viruses which were recognised poorly by post-infection ferret antiserum raised against B/Washington/02/2019, the 2021-2022 northern hemisphere vaccine virus [1]. However, the V1A.3a.2 viruses were recognised well (with HI titres of at least 160 with the antiserum raised against the egg-propagated variant with HA1 G141R substitution) by antisera raised against B/Austria/1359417/2021, the recommended vaccine virus for southern hemisphere 2022 and 2023, and northern hemisphere 2022-2023 influenza seasons [2, 4, 3]. This was observed for the 12 subgroup V1A.3a.2 viruses characterised antigenically since the July report (Tables 6-1 to 6-3). All test viruses were recognised well, within twofold of the homologous titres, by post-infection ferret antisera raised against cell culture-propagated and egg-propagated B/Austria/1359417/2021 viruses carrying HA1 G141. In contrast the B/Austria/1359417/2021 vaccine virus, which has an ʻegg-adaptationʼ HA1 G141R amino acid _____ 4 European Centre for Disease Prevention and Control. Influenza virus characterisation, summary Europe, September 2018. Stockholm: ECDC; 2018. Available from: https://ecdc.europa.eu/sites/portal/files/documents/ECDC-Flu-Characterisation-Report-Sep-2018.pdf WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 25 substitution, induced a high homologous titre (5120) antiserum and all test viruses showed a drop in recognition of at least eightfold compared to the homologous titre, but all test viruses reacted with a titre of at least 160, well above the threshold of 40 that has been determined as the cut-off for a protective effect. All three cell culture- propagated subclade V1A.3 viruses from the Netherlands, all of which contained a HA1 G184R amino acid substitution, were poorly recognised by the hyperimmune sheep serum raised against B/Brisbane/60/2008 and all the post-infection ferret antisera except for that raised against cell culture-propagated B/Netherlands/11267/2022 (Table 6-1). Conversely, the three egg-propagated V1A.3 viruses from the Netherlands were well recognised by the sheep hyperimmune serum, less efficiently by the post-infection ferret antiserum raised against cell culture- propagated B/Netherlands/11267/2022 and somewhat better by ferret antisera raised against B/Colorado/06/2017 (V1A.1) and B/Washington/02/2019 (V1A.3) (Table 6-3). The latter is related to loss of a HA1 glycosylation sequon at positions 194-196 (V1A.3 numbering) or 197-199 (V1A numbering) on adaptation to replication in hensʼ eggs. Influenza B/Yamagata-lineage It is assumed that no B/Yamagata-lineage viruses have been detected after March 2020 as no sequences for such viruses with collection dates after this had been released is GISAID as of 28 September 2022. Figure 5 is repeated from the September 2021 report. All sequences fell in genetic clade Y3, the B/Wisconsin/1/2010– B/Phuket/3073/2013 clade, within a subgroup defined by HA1 L172Q and M251V amino acid substitutions compared to B/Phuket/3073/2013 which was recommended for inclusion in quadrivalent vaccines for the 2021-2022 and 2022-2023 northern and, 2022 and 2023 southern hemisphere seasons [1, 3, 2, 4]. Some sub-clustering of sequences, defined by specific amino acid substitutions (e.g., HA1 N164K, K211R, D229N or D232N [introducing a potential N-linked glycosylation site] sometimes with R48K), had occurred. As noted in previous characterisation reports, none of these amino acid substitutions have any obvious antigenic effects based on HI assays using post- infection ferret antisera raised against egg-propagated B/Phuket/3073/2013. Of the four samples shared with WIC by the United Kingdom (Scotland: Table 3) only one yielded good sequence which showed it to be associated with Live Attenuated Influenza Vaccine (LAIV). A concerted effort by all NICs of GISRS is required to identify B/Yamagata-lineage viruses for detailed characterisation to determine if there are any in circulation that are not LAIV-related. WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 26 Figure 4a. Phylogenetic comparison of B/Victoria-lineage HA genes (GISAID/WIC, July 2022) WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 27 Figure 4b. Phylogenetic comparison of B/Victoria-lineage HA genes (GISAID/WIC, Sept 2022) WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 28 Table 6-1. Antigenic analysis of influenza B/Victoria-lineage viruses by HI N EW N EW Vi ru se s O th er C ol le ct io n Pa ss ag e B /B ris B /C ol or ad o B /W as h' to n B /N et h B /C IV B /P ar is B /G -B ai yi n B /A us tr ia B /A us tr ia B /A us tr ia B /A us tr ia in fo rm at io n da te hi st or y 60 /0 8 06 /1 7 02 /1 9 11 26 7/ 22 94 8/ 20 98 78 /2 0 12 81 /2 1 13 59 41 7/ 21 13 59 41 7/ 21 13 59 41 7/ 21 13 59 41 7/ 21 Pa ss ag e hi st or y Eg g Eg g Eg g M D C K M D C K M D C K M D C K M D C K Eg g G 14 1 Eg g G 14 1R Eg g G 14 1R Fe rr et n um be r Sh 5 39 , 5 40 , 54 3, 5 44 , 5 70 , 57 1, 5 74 *1 ,3 F1 1/ 18 *2 F2 0/ 20 *2 F 29 /2 2* 1 F0 8/ 21 *5 F1 2/ 21 *1 F0 8/ 22 *1 N IB F 01 /2 1* 1 F1 5/ 21 *1 F 44 /2 1* 1 F 30 /2 2* 1 G en et ic g ro up V1 A V1 A. 1 V1 A. 3 V1 A. 3 V1 A. 3a .1 V1 A. 3a .2 V1 A. 3a .2 V1 A. 3a .2 V1 A. 3a .2 V1 A. 3a .2 V1 A. 3a .2 R EF ER EN C E VI R U SE S B /B ris ba ne /6 0/ 20 08 V1 A 20 08 -0 8- 04 E4 /E 4 25 60 16 0 40 < < < < < < < < B /C ol or ad o/ 06 /2 01 7 V1 A. 1 20 17 -0 2- 05 E5 /E 2 12 80 64 0 80 < < < < < < < < B /W as hi ng to n/ 02 /2 01 9 V1 A. 3 20 19 -0 1- 19 E3 /E 3 64 0 16 0 16 0 < < < < < < < < B /N et he rla nd s/ 11 26 7/ 20 22 G 18 4R V1 A. 3 20 22 -0 4- 14 M D C K -M IX /M D C K 1 40 10 < 32 0 < < < < < < < B /C ot e d' Iv oi re /9 48 /2 02 0 V1 A. 3a .1 20 20 -0 5- 28 M D C K 4 32 0 40 40 40 64 0 40 40 16 0 80 80 40 B /P ar is /9 87 8/ 20 20 V1 A. 3a .2 20 20 -1 1- 20 M D C K 2 64 0 80 10 < 16 0 64 0 16 0 12 80 12 80 32 0 16 0 B /G an su -B ai yi n/ 12 81 /2 02 1 V1 A. 3a .2 20 21 -0 4- 13 C 1/ C 1/ M D C K 2 64 0 40 < 40 16 0 64 0 32 0 12 80 12 80 32 0 32 0 B /A us tr ia /1 35 94 17 /2 02 1 V1 A. 3a .2 20 21 -0 1- 09 SI AT 1/ M D C K 4 64 0 80 10 < 16 0 64 0 32 0 12 80 12 80 32 0 32 0 B /A us tr ia /1 35 94 17 /2 02 1 Is ol at e 2 G 14 1 V1 A. 3a .2 20 21 -0 1- 09 E3 /E 5 64 0 40 10 40 32 0 64 0 32 0 25 60 12 80 64 0 64 0 B /A us tr ia /1 35 94 17 /2 02 1 Is ol at e 2 G 14 1R V1 A. 3a .2 20 21 -0 1- 09 E3 /E 5 32 0 40 < 40 32 0 32 0 32 0 12 80 12 80 25 60 >5 12 0 TE ST V IR U SE S B /N et he rla nd s/ 11 26 6/ 20 22 G 18 4R V1 A. 3 20 22 -0 4- 13 M D C K 1 40 10 < 16 0 < < < < < < < B /N et he rla nd s/ 11 30 3/ 20 22 G 18 4R V1 A. 3 20 22 -0 4- 19 M D C K 1 80 10 < 32 0 < < < < < < < B /N et he rla nd s/ 11 27 9/ 20 22 G 18 4R V1 A. 3 20 22 -0 4- 26 M D C K 1 80 10 10 16 0 < < < < < < < B /L yo n/ C H U /R 22 .1 95 .1 7/ 20 22 V1 A. 3a .2 20 22 -0 4- 09 M D C K x/ M D C K 1 12 80 80 20 40 16 0 64 0 32 0 12 80 12 80 64 0 32 0 B /U kr ai ne /4 02 /2 02 2 V1 A. 3a .2 20 22 -0 4- 18 M D C K 1 12 80 80 10 40 16 0 64 0 32 0 12 80 12 80 64 0 32 0 B /B el gi um /H 05 60 /2 02 2 V1 A. 3a .2 20 22 -0 5- 04 M D C K 1/ M D C K 1 64 0 40 < 40 16 0 32 0 16 0 12 80 12 80 32 0 16 0 B /N ic e/ 88 2/ 20 22 V1 A. 3a .2 20 22 -0 5- 05 M D C K x/ M D C K 1 64 0 80 10 40 16 0 32 0 32 0 12 80 12 80 32 0 32 0 B /U kr ai ne /4 07 /2 02 2 V1 A. 3a .2 20 22 -0 5- 30 M D C K 1 12 80 16 0 10 40 16 0 64 0 32 0 12 80 12 80 64 0 32 0 * Va cc in e SH 2 02 0 N H 2 02 0- 21 SH 2 02 1 N H 2 02 1- 22 SH 2 02 3 SH 2 02 2 N H 2 02 2- 23 Va cc in e H ae m ag gl ut in at io n in hi bi tio n tit re Po st -in fe ct io n fe rr et a nt is er um Su pe rs cr ip ts re fe r t o an tis er um p ro pe rt ie s (< re la te s to th e lo w es t d ilu tio n of a nt is er um u se d) : 1 < = < 40 ; 2 < = < 10 ; 3 h yp er im m un e sh ee p se ru m ; 4 < = < 20 ; 5 < = < 80 ; N D = N ot D on e WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 29 Table 6-2. Antigenic analysis of influenza B/Victoria-lineage viruses by HI V iru se s O th er C ol le ct io n Pa ss ag e B /B ris B /C ol or ad o B /W as h' to n B /N et h B /C IV B /P ar is B /G -B ai yi n B /A us tr ia B /A us tr ia B /A us tr ia in fo rm at io n da te hi st or y 60 /0 8 06 /1 7 02 /1 9 11 26 7/ 22 94 8/ 20 98 78 /2 0 12 81 /2 1 13 59 41 7/ 21 13 59 41 7/ 21 13 59 41 7/ 21 Pa ss ag e hi st or y Eg g Eg g Eg g M D C K M D C K M D C K M D C K M D C K Eg g G 14 1 Eg g G 14 1R Fe rr et n um be r Sh 5 39 , 5 40 , 54 3, 5 44 , 5 70 , 57 1, 5 74 *1 ,3 F1 1/ 18 *2 F2 0/ 20 *2 F 29 /2 2* 1 F0 8/ 21 *5 F1 2/ 21 *1 F0 8/ 22 *1 N IB F 01 /2 1* 1 F1 5/ 21 *1 F 44 /2 1* 1 G en et ic g ro up V1 A V1 A. 1 V1 A. 3 V1 A. 3 V1 A. 3a .1 V1 A. 3a .2 V1 A. 3a .2 V1 A. 3a .2 V1 A. 3a .2 V1 A. 3a .2 R EF ER EN C E VI R U SE S B /B ris ba ne /6 0/ 20 08 V1 A 20 08 -0 8- 04 E4 /E 4 12 80 16 0 40 < < < < < < < B /C ol or ad o/ 06 /2 01 7 V1 A. 1 20 17 -0 2- 05 E5 /E 2 12 80 64 0 80 < < < < < < < B /W as hi ng to n/ 02 /2 01 9 V1 A. 3 20 19 -0 1- 19 E3 /E 3 64 0 16 0 16 0 < < < < < < < B /N et he rla nd s/ 11 26 7/ 20 22 G 18 4R V1 A. 3 20 22 -0 4- 14 M D C K -M IX /M D C K 1 40 10 < 32 0 < < < < < < B /C ot e d' Iv oi re /9 48 /2 02 0 V1 A. 3a .1 20 20 -0 5- 28 M D C K 4 32 0 40 40 40 64 0 40 40 16 0 80 80 B /P ar is /9 87 8/ 20 20 V1 A. 3a .2 20 20 -1 1- 20 M D C K 2 64 0 80 10 < 16 0 64 0 16 0 12 80 12 80 32 0 B /G an su -B ai yi n/ 12 81 /2 02 1 V1 A. 3a .2 20 21 -0 4- 13 C 1/ C 1/ M D C K 2 64 0 40 < 40 16 0 64 0 64 0 12 80 12 80 32 0 B /A us tr ia /1 35 94 17 /2 02 1 V1 A. 3a .2 20 21 -0 1- 09 SI AT 1/ M D C K 4 64 0 80 10 < 16 0 64 0 32 0 25 60 12 80 32 0 B /A us tr ia /1 35 94 17 /2 02 1 Is ol at e 2 G 14 1 V1 A. 3a .2 20 21 -0 1- 09 E3 /E 5 64 0 40 10 40 32 0 64 0 32 0 25 60 25 60 64 0 B /A us tr ia /1 35 94 17 /2 02 1 Is ol at e 2 G 14 1R V1 A. 3a .2 20 21 -0 1- 09 E3 /E 5 32 0 40 < 40 32 0 32 0 32 0 12 80 12 80 25 60 TE ST V IR U SE S B /M os co w /R II- 01 /2 02 2 V1 A. 3a .2 20 22 -0 4- 28 M D C K 3/ M D C K 1 12 80 80 10 80 32 0 64 0 64 0 25 60 25 60 64 0 B /S . P et er sb ur g/ R II- 09 /2 02 2 V1 A. 3a .2 20 22 -0 5- 13 M D C K 1/ M D C K 1 12 80 80 20 80 32 0 64 0 64 0 25 60 25 60 64 0 B /S . P et er sb ur g/ R II- 11 /2 02 2 V1 A. 3a .2 20 22 -0 5- 25 M D C K 1/ M D C K 1 12 80 80 10 40 32 0 64 0 32 0 25 60 25 60 32 0 B /S . P et er sb ur g/ R II- 15 /2 02 2 V1 A. 3a .2 20 22 -0 5- 26 M D C K 1/ M D C K 1 12 80 16 0 20 80 32 0 64 0 64 0 12 80 25 60 64 0 B /S . P et er sb ur g/ R II- 13 /2 02 2 V1 A. 3a .2 20 22 -0 6- 06 M D C K 1/ M D C K 1 12 80 80 20 80 16 0 64 0 32 0 12 80 12 80 32 0 * Va cc in e SH 2 02 0 N H 2 02 0- 21 SH 2 02 1 N H 2 02 1- 22 SH 2 02 3 N H 2 02 2- 23 H ae m ag gl ut in at io n in hi bi tio n tit re Po st -in fe ct io n fe rr et a nt is er um Su pe rs cr ip ts re fe r t o an tis er um p ro pe rt ie s (< re la te s to th e lo w es t d ilu tio n of a nt is er um u se d) : 1 < = < 40 ; 2 < = < 10 ; 3 h yp er im m un e sh ee p se ru m ; 4 < = < 20 ; 5 < = < 80 ; N D = N ot D on e Va cc in e SH 2 02 2 WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 30 Table 6-3. Antigenic analysis of influenza B/Victoria-lineage viruses by HI N EW Vi ru se s O th er C ol le ct io n Pa ss ag e B /B ris B /C ol or ad o B /W as h' to n B /N et h B /C IV B /P ar is B /G -B ai yi n B /A us tr ia B /A us tr ia B /A us tr ia in fo rm at io n da te hi st or y 60 /0 8 06 /1 7 02 /1 9 11 26 7/ 22 94 8/ 20 98 78 /2 0 12 81 /2 1 13 59 41 7/ 21 13 59 41 7/ 21 13 59 41 7/ 21 Pa ss ag e hi st or y Eg g Eg g Eg g M D C K M D C K M D C K M D C K M D C K Eg g G 14 1 Eg g G 14 1R Fe rr et n um be r Sh 5 39 , 5 40 , 54 3, 5 44 , 5 70 , 57 1, 5 74 *1 ,3 F4 4/ 18 *2 F2 0/ 20 *2 F 29 /2 2* 1 F0 8/ 21 *5 F1 2/ 21 *1 F0 8/ 22 *1 N IB F 01 /2 1* 1 F1 5/ 21 *1 F 44 /2 1* 1 G en et ic g ro up V1 A V1 A. 1 V1 A. 3 V1 A. 3 V1 A. 3a .1 V1 A. 3a .2 V1 A. 3a .2 V1 A. 3a .2 V1 A. 3a .2 V1 A. 3a .2 R EF ER EN C E VI R U SE S B /B ris ba ne /6 0/ 20 08 V1 A 20 08 -0 8- 04 E4 /E 4 12 80 16 0 40 < < < < < < < B /C ol or ad o/ 06 /2 01 7 V1 A. 1 20 17 -0 2- 05 E5 /E 2 12 80 64 0 40 < < < < < < < B /W as hi ng to n/ 02 /2 01 9 V1 A. 3 20 19 -0 1- 19 E3 /E 3 12 80 16 0 80 40 < < < < < < B /N et he rla nd s/ 11 26 7/ 20 22 G 18 4R V1 A. 3 20 22 -0 4- 14 M D C K -M IX /M D C K 1 40 10 < 32 0 < < < < < < B /C ot e d' Iv oi re /9 48 /2 02 0 V1 A. 3a .1 20 20 -0 5- 28 M D C K 4 32 0 40 40 40 64 0 80 40 16 0 16 0 80 B /P ar is /9 87 8/ 20 20 V1 A. 3a .2 20 20 -1 1- 20 M D C K 2 64 0 80 10 40 16 0 64 0 32 0 12 80 12 80 32 0 B /G an su -B ai yi n/ 12 81 /2 02 1 V1 A. 3a .2 20 21 -0 4- 13 C 1/ C 1/ M D C K 2 64 0 40 < < 16 0 32 0 32 0 12 80 12 80 32 0 B /A us tr ia /1 35 94 17 /2 02 1 V1 A. 3a .2 20 21 -0 1- 09 SI AT 1/ M D C K 4 64 0 40 < 40 16 0 32 0 32 0 12 80 12 80 32 0 B /A us tr ia /1 35 94 17 /2 02 1 Is ol at e 2 G 14 1 V1 A. 3a .2 20 21 -0 1- 09 E3 /E 5 64 0 20 < 40 16 0 32 0 32 0 25 60 12 80 32 0 B /A us tr ia /1 35 94 17 /2 02 1 Is ol at e 2 G 14 1R V1 A. 3a .2 20 21 -0 1- 09 E3 /E 5 32 0 20 < 40 32 0 32 0 32 0 12 80 12 80 25 60 TE ST V IR U SE S B /N et he rla nd s/ 10 89 4/ 20 22 G 18 4R , T 19 6( 19 9) A (-c ho ) V1 A. 3 20 22 -0 4- 02 E3 (A m 1A L2 ) 64 0 40 20 40 < < < < < < B /N et he rla nd s/ 11 26 4/ 20 22 G 18 4R , N 19 4( 19 7) S (-c ho ) V1 A. 3 20 22 -0 4- 13 E4 (A m 1A L3 ) 64 0 16 0 80 80 < < < < < < B /N et he rla nd s/ 11 26 4/ 20 22 G 18 4R , N 19 4( 19 7) S (-c ho ) V1 A. 3 20 22 -0 4- 13 E4 (A m 2A L2 ) 12 80 16 0 40 80 < < < < < < B /S . P et er sb ur g/ R II- 04 /2 02 2 V1 A. 3a .2 20 22 -0 3- 10 M D C K 3/ M D C K 1 64 0 40 < 40 16 0 32 0 32 0 12 80 12 80 32 0 B /S . P et er sb ur g/ R II- 06 /2 02 2 V1 A. 3a .2 20 22 -0 4- 27 M D C K 3/ M D C K 1 64 0 40 < 40 16 0 32 0 32 0 12 80 12 80 32 0 * Va cc in e SH 2 02 0 N H 2 02 0- 21 SH 2 02 1 N H 2 02 1- 22 N H 2 02 2- 23 SH 2 02 3 H ae m ag gl ut in at io n in hi bi tio n tit re Po st -in fe ct io n fe rr et a nt is er um Su pe rs cr ip ts re fe r t o an tis er um p ro pe rt ie s (< re la te s to th e lo w es t d ilu tio n of a nt is er um u se d) : Va cc in e 1 < = < 40 ; 2 < = < 10 ; 3 h yp er im m un e sh ee p se ru m ; 4 < = < 20 ; 5 < = < 80 ; N D = N ot D on e SH 2 02 2 WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 31 Figure 5. Phylogenetic comparison of B/Yamagata-lineage HA genes (GISAID, September 2021) WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 32 Summaries of data submitted to TESSy WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 33 Genetic characterisation 5 355 viruses detected over the course of the 2021-2022 season (weeks 40/2021-39/2022) were genetically characterised: • Of 429 A(H1N1)pdm09 viruses, 373 belonged to clade 6B.1A.5a.1 (represented by A/Guangdong- Maonan/SWL1536/2019) and 56 belonged to clade 6B.1A.5a.2 (represented by A/Victoria/2570/2019). • Of 4 818 A(H3N2) viruses, 4 766 belonged to the ʻBangladesh-likeʼ clade (3C.2a1b.2a.2) represented by A/Bangladesh/4005/2020, three to the ʻCambodia-likeʼ clade (3C.2a1b.2a.1) and 21 were attributed to clade 3C.2a1b.1a (represented by A/Denmark/3264/2019). Twenty-eight were not attributed to a listed subgroup. • Of 108 influenza B viruses, 101 were ascribed to the B/Victoria-lineage: 65 were B/Austria/1359417/2021-like (V1A.3a.2), 33 were B/Washington/02/2019-like (V1A.3) and three were not attributed to a listed subgroup. Of the seven B/Yamagata-lineage viruses, four were B/Phuket/3073/2013-like (Y3) and three were not ascribed to a clade. Note: of the B/Yamagata-lineage specimens shared with WIC, all were from children and those that yielded gene sequence were derived from Live Attenuated Influenza Vaccine (LAIV). Antiviral susceptibility Up to week 20/2022, 2 547 viruses were assessed for susceptibility to neuraminidase inhibitors (NAIs): 1 715 A(H3), 258 A(H1)pdm09 and 54 B virus were assessed genotypically, and 476 A(H3), 31 A(H1)pdm09 and 13 B viruses were assessed phenotypically. Susceptibility to the PA inhibitor baloxavir marboxil was assessed genotypically for 1 792 viruses: 1 528 A(H3), 227 A(H1)pdm09 and 37 B viruses. For weeks 21-30/2022, 18 viruses were assessed for susceptibility to NAIs and baloxavir marboxil. For weeks 35-39/2022 a further14 viruses were assessed for susceptibility to NAIs and baloxavir marboxil. Phenotypically no viruses with reduced susceptibility were identified. Genotypically, two A(H3) viruses showed PA amino acid substitutions potentially associated with reduced susceptibility to baloxavir marboxil and one A(H1)pdm09 virus with potential highly reduced inhibition by oseltamivir was identified. At the WIC, 1 194 influenza viruses detected within the WHO European Region during the 2021-2022 season have been assessed phenotypically against oseltamivir and zanamivir: 186 A(H1)pdm09, 915 A(H3) and 93 B/Victoria- lineage. All viruses showed normal inhibition (NI) by both NAIs and PA gene sequences from three A(H3) viruses had markers (amino acid substitutions) associated with reduced susceptibility to baloxavir marboxil, E23G (n = 1) and L28P (n = 2) respectively. Animal influenza and zoonotic events WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 34 Influenza A(H7N9) virus On 1 April 2013, the WHO Global Alert and Response System [5] reported that the China Health and Family Planning Commission had notified WHO of three cases of human infection with influenza A(H7N9). Increased numbers of cases were reported over the course of the following seasons, and cases were reported in 2017, including the fifth (2016-17) and largest wave to date, which included the emergence of highly pathogenic avian influenza (HPAI) strains that have caused some zoonoses, although few human cases were reported during the 2017-18 season [6]. Current risk assessments for influenza at the human-animal interface can be found on WHOʼs website https://www.who.int/teams/global-influenza-programme/avian-influenza/monthly-risk-assessment- summary (accessed 06 October 2022). The assessment published on 27 June 2022 indicated that there had been no publicly available reports from animal health authorities in China or other countries on influenza A(H7N9) virus detections in animals in recent months [7]. On 01 June 2022 the Food and Agricultural Organization of the United Nations announced that it was discontinuing monthly H7N9 updates as there had been no notifications of avian infections since October 2020. The most recent human case was detected in mid-March 2019 [8]. The latest overview of avian influenza by ECDC in collaboration with the European Food Safety Authority and the EU Reference Laboratory for Avian Influenza was approved on 28 September 2022 and can be found on ECDCʼs website [9]. WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 35 WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 36 Influenza A(H5) virus The most recent monthly risk assessment of influenza at the human-animal interface was published by WHO on 30 August 2022. Since the previous risk assessment on 27 June 2022, one human case of infection with an A(H5N6) avian influenza virus was reported by China [7]. The case was in a 6-year-old female with no underlying medical conditions who had disease onset on 30 July 2022, was hospitalised with severe pneumonia and passed away on 24 April. The second case was in a 58-year-old male who had disease onset on 02 June 2022, was hospitalised with severe pneumonia and was still in a severe condition at the time of reporting. The patient was exposed to poultry at a live poultry market and no family members had developed disease symptoms at the time of reporting. The most recent confirmed case of human infection with an A(H5N1) virus was reported by England and a full report into the investigation of this case has been published [10]. The latest collaborative report from ECDC and the European Food Safety Authority (EFSA), reported 788 highly pathogenic avian influenza (HPAI) A(H5) detections between 11 June and 09 September 2022, 56 in poultry, 710 in wild birds and 22 in captive birds [9]. Detections occurred in 16 European countries and high mortality was observed in colony-breeding seabird species along the northwest coast of Europe involving HPAI A(H5N1). Overall, the HPAI epidemic season in 2021-2022 is the largest so far observed in Europe with 2 467 outbreaks in poultry and 47.7 million birds culled, 187 outbreaks in captive birds, and 3 573 detections in wild birds. Genetic analyses indicated that the circulating viruses belonged to clade 2.3.4.4b. Such viruses have been circulating in Europe since October 2020 and now exist as seven genotypes, three of which were identified over the summer period. The risk of human infection was assessed as low for the general population in EU/EEA countries, and low to medium for occupationally exposed persons. According to reports compiled by the Food and Agricultural Organization of the United Nations (FAO) as of 28 September 2022, various highly pathogenic avian influenza (HPAI) subtypes continued to be detected in wild and/or domestic birds in Africa, Americas, Asia and Europe, and since 24 August 2022 a total of 1 729 HPAI outbreaks (19 H5Nx, 1 706 H5N1, two H5N2, one H5N8 and one HPAI not confirmed as H5) and no low pathogenic avian influenza (LPAI) outbreaks had been reported [11]. HPAI A(H5) viruses have also been detected in wild mammal species in Europe and North America, with some viruses showing genetic markers of adaptation to replication in mammals. WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 37 Influenza A(H9N2) virus Since the previous WHO risk assessment on 27 June 2022, China reported one case of H9N2 infection in a six-month old male with onset of symptoms on 01 August. He had mild disease, was hospitalized, and made a full recovery [7]. Poultry exposure was reported, environmental samples from the poultry market were A(H9)-positive and no family members had developed symptoms at the time of reporting. Public Health England has published an updated risk assessment for avian influenza A(H9N2) [12]. Avian influenza A(H9N2) viruses are enzootic in poultry in Asia and increasingly reported in poultry in Africa. WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 38 Other influenza zoonotic events Since the previous WHO update on 27 June 2022 the United States of America (USA) reported zoonoses involving swine influenza variant viruses [7]. Two cases of A(H1N2)v infection were reported in patients under 18 years of age, one in Oregon and the other in Ohio. Both patients recovered, one reported potential swine exposure at an agricultural fair, and in neither case was transmission to close human contacts suspected. Three cases of A(H3N2)v infection resulting from attendance of an agricultural fair in West Virginia were reported. None of the patients were hospitalized and all made a full recovery. While human-to-human transmission at the fair cannot be ruled out, no sustained human-to-human transmission was identified. Gene sequencing showed the zoonotic viruses to be closely related to viruses known to be circulating in pigs in the USA. WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 39 WHO Collaborating Centre reports A description of results generated by the London WHO Collaborating Centre at the WIC and used at the September 2022 WHO VCM (19-22 September 2022 for seasonal influenza viruses), and previous ones, can be found at https://www.crick.ac.uk/partnerships/worldwide-influenza-centre/annual-and-interim-reports (accessed 07 October 2022). WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 40 Note on the figures The phylogenetic trees were constructed using RAxML, drawn using FigTree, and annotated using Adobe Illustrator. The bars indicate the proportion of nucleotide changes between sequences. Reference strains are viruses to which post-infection ferret antisera have been raised. The colours indicate the month(s) of sample collection. Sequences for many viruses from non-WHO Europe countries were recovered from the GISAID EpiFluTM database. We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from the GISAID EpiFluTM database, which were downloaded for use in the preparation of this report (all submitters of data may be contacted directly via the GISAID website), along with all laboratories who submitted sequences directly to WHO CC London. WHO EUROPE SURVEILLANCE REPORT Influenza virus characterisation – Summary Europe, September 2022 41 References5 1. Recommended composition of influenza virus vaccines for use in the 2021-2022 northern hemisphere influenza season. Weekly Epidemiological Record 19 March 2021, vol. 96, (11):77-88. Geneva: World Health Organization; 2021 (https://reliefweb.int/sites/reliefweb.int/files/resources/WER9611-eng-fre.pdf). 2. Recommended composition of influenza virus vaccines for use in the 2022 southern hemisphere influenza season. 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Guidance, risk assessment of avian influenza A(H9N2) update, 9 August 2021. UK.gov: PHE; 2021 (https://www.gov.uk/government/publications/risk-assessment-of-avian-influenza-ah9n2/risk- assessment-of-avian-influenza-ah9n2). _____ 5 All references except reference 11 accessed on 14 September 2022. European Centre for Disease Prevention and Control (ECDC) Gustav den III:s Boulevard 40, SE-169 73, Solna, Sweden Tel. +46 858 60 10 00 Fax +46 858 60 10 01 www.ecdc.europa.eu Contact us publications@ecdc.europa.eu Follow us on Twitter @ECDC_EU Like our Facebook page www.facebook.com/ECDC.EU World Health Organization Regional Office for Europe UN City, Marmorvej 51, DK-2100 Copenhagen Ø, Denmark Tel. +45 45 33 70 00 Fax +45 45 33 70 01 www.who.int/europe Contact us eurocontact@who.int Follow us on Twitter @WHO_EUROPE Like our Facebook page www.facebook.com/WHOEurope