Problems in the determination of the antigenic content of influenza vaccines

Discussion Papers-Session III Problems in the Determination of the Antigenic Content of Influenza Vaccines by A. V. HENNESSY a There has recently been considerable concern about the antigenic content of certain influenza virus vaccines. In consequence, a collaborative study was organized between the Virus Laboratory, School of Public Health, University of Michigan, Ann Arbor, and Dr Tauraso's laboratory at the Division of Biologics Standards, National Institutes of Health, Bethesda, Md., to ascertain whether more exact standards for vaccine release could be established and whether it was reasonable to expect other laboratories to meet these standards. Thirty-three vaccine preparations, the CCA units of which had been determined by the Miller-Stanley method at the Division of Biologics Standards, were sent under code to the Virus Laboratory, Ann Arbor. There, the CCA values were determined for each preparation by the new Miller method. The results were returned to the Division of Biologics Standards (DBS), where the code was broken. Twenty-three preparations were monovalent or bivalent vaccines containing the Hong Kong strain, while 10 were regular military-issue polyvalent vaccines not con- taining Hong Kong virus. In Ann Arbor the standard used to measure chicken-cell agglutination was the DBS CCA-10 monovalent standard for Hong Kong vaccine, containing 400 CCA units per ml. At the Division of Biologics Standards the same standard was employed for the Hong Kong vaccine but the DBS 67M military polyvalent standard, containing 1000 CCA units per ml, was used for monitoring the military polyvalent vaccine. a School of Public Health, University of Michigan, Ann Arbor, Mich., USA. The average standard deviation of the titre for the 23 Hong Kong vaccines measured in Ann Arbor is 13 %, while that found at the Division of Biologics Standards was 15%. For the polyvalent vaccine the average standard deviation of the titre was 12% for the Ann Arbor series and 21 % for the Division of Biologics Standards series. The over-all average standard deviation was 13% for the Ann Arbor CCA determinations and 17% for those of the Division of Biologics Standards. There is 91 % agreement when the limit of ± 25% difference in CCA values is used and 73% agreement when as narrow a limit as ± 15% difference is employed. The close agreement between the two laboratories is notable since the two procedures employed are quite different. The Miller method uses a fixed range of transmission values that the standard must show at the time the values for the unknown are read. This means that the test is not read at a fixed time, while the Miller-Stanley procedure uses a fixed time period for settling before the test is read. The Miller procedure is a reproducible method for the determina- tion of the CCA values and, since the calculations are somewhat simpler, may be more desirable than the Miller-Stanley procedure. The findings indicate that the antigenic content of influenza vaccines, as defined by photometric standards, can be measured reproducibly in different laboratories and in consequence delivery of a more uniform product can be expected when CCA values are prescribed as an additional component of vaccine specifications. 2404A -553-