Experience in Yugoslavia with live influenza vaccine prepared from an attenuated A2/Hong Kong/68 strain

608 DISCUSSION PAPERS-SESSION IV Experience in Yugoslavia with Live Influenza Vaccine Prepared from an Attenuated A2/Hong Kong/68 Strain by D. IKIC a The appearance of the Hong Kong variant of influenza A2 provided an opportunity to ascertain whether it is possible, when a major antigenic shift of influenza virus occurs, to prepare a sufficient amount of live vaccine from the new strain in good time and to organize an effective large-scale vaccina- tion campaign. In the middle of October 1968 the A2/Aichi/2/68 strain was received in the Institute of Immunology, Zagreb, and in November b its attenuation was undertaken by passing it in the chick-embryo allan- tois at a temperature of 350C.c The first experimental lots of vaccine were pre- pared from the 8th and the 12th allantoic passages and tested for reactions in the field. With the vaccine prepared from the 8th passage the reactions were unexpectedly pronounced in the majority of vaccinees, particularly in sensitive per- sons. The vaccine prepared from the 12th allantoic passage was diluted so that the virus concentration per dose amounted to 5 log for adults and 4 log for children (7-16 years old). The intensity of post- vaccinal reactions was evaluated on the basis of the rise of temperature which was taken once daily over 4 days following vaccination. The reactions were mild and there was almost no difference between the control group and the vaccinated group. By the middle of January 1969, 10 million doses of vaccine had been prepared and by the end of February nearly 1 million people had been vaccin- ated. About 100 000 doses of vaccine were used for the mass vaccination of schoolchildren. In addition 11/2 mnillion doses of live freeze-dried influenza vaccine prepared from the strain A2/L-Z/12/65 had been distributed before the vaccine prepared from the attenuated A2/Hong Kong strain became available. Hong Kong influenza broke out in epidemic form in Yugoslavia in 1969 in one region only and this a Institute of Immunology, Zagreb, Yugoslavia. b Influenza epidemics in Yugoslavia usually begin at the end of February and end in the first half of April. c Ikid, D. et al.: Attenuation of A2 (Hong Kong) variant of influenza virus; paper presented at the Symposium on Acute Respiratory Diseases held in Zagreb on 1-2 October 1969. provided an opportunity to study the effectiveness of live influenza vaccine in 3 towns in which the employees of 5 large establishments were vaccinated. The protection of those vaccinated with the strains A2/L-Z/12/65 and A2/A-Z/11/68 (Hong Kong variant) was highly significant in all 5 establishments (P < 0.001). During the past 7 years several field trials of the effectiveness of live influenza vaccine have been carried out in Yugoslavia, d, e, f and they have pro- vided definitive data on the high degree of protec- tion that vaccination can confer. The results ob- tained in 1969 agree with the experience of earlier years. The degree of effectiveness ofimmunization against influenza by the use of live vaccine depends on the proportion of vaccinated individuals in an observed population group. From data collected in 1964 it became evident that there was a constant and distinct rise in effectiveness positively correlated with the proportion of the population immunized (see the table). The association between the percentage of vac- cinated employees and the percentage of employees who fell ill was highly significant (P < 0.001), indicating that the incidence of influenza depended upon the number of vaccinated persons in an estab- lishment. To obtain a severe reduction in the incid- ence of influenza, 80% or more of the population should be vaccinated. The attenuation of a new virus strain and the preparation of vaccine depend in the first place on the quickest possible notification to manufacturing institutes about the appearance of a new variant and on its prompt delivery to them for attenuation. It would be useful if an international list of institutes engaged in the large-scale preparation of live influenza vaccine could be centrally compiled and if the compiler would serve as the supplier of d Ikic, D. et al. (1966) Rad. Immunol. Zav., 5-6, 1-18. e Ikic, D. et al.: Study of the protective effect of live influenza vaccine (1964-68); paper presented at the Sympo- sium on Acute Respiratory Diseases held in Zagreb on 1-2 October 1969. f Ikic, D. et al.: Experiences with live influenza vaccine in 1969; paper presented at the Symposium on Acute Res- piratory Diseases held in Zagreb on 1-2 October 1969. 2411B EXPERIENCE IN YUGOSLAVIA WITH ATTENUATED HONG KONG INFLUENZA VACCINE INFLUENCE OF THE PROPORTION OF THE POPULATION VACCINATED ON THE REDUCTION OF INFLUENZA a Vaccinated FNo. of pros Influenza cases IncidenceGroup M in group __No _ _____relativeto Group Vgroup ~~No. (%) I 80 33428 844 2.52 11.2 11 60-80 14091 730 5.18 23.1 111 40-60 16404 1 905 11.61 51.8 IV 40 5 559 754 13.56 60.5 V 0 17 723 3 976 22.43 100.0 a Data from 1964. strains and as mediator in the exchange of inform- ation on virus attenuation between manufacturing institutes. When a new antigenic variant appears, the only way to provide a sufficient quantity of live vaccine rapidly is to use as few passages as possible for virus attenuation and a small number of virus particles per dose. This can be achieved with a relatively small number of RIF-free eggs. A thou- sand such eggs will yield 5 million doses of vaccine with a virus concentration of 10-5/0.1 ml. For this purpose, however, the virus should be well charac- terized in the laboratory to ensure mild reactions and high immunogenicity. So far this has not been possible because of the lack of markers, and here lies the main drawback of live influenza vaccines. 19 609