Morphology and antigenicity studies on reassortant influenza (H3N2) viruses for use in inactivated vaccines

Three influenza A (H3N2) reassortant whole virus vaccine strains with differing antibody-inducing capacities in hamsters were investigated morphologically and antigenically. Although initial measurements of virion circumference, from electron micrographs of vaccine preparations, suggested a relationship of small virion size with low immunogenicity, subsequent immunization with, and morphological investigation of, vaccine virions separated on sucrose gradients, failed to obtain populations whose antibody-inducing capacity clearly correlated with constituent virion density, size, morphology or integrity. However, antigenic investigation using single radial haemolysis (SRH) and monoclonal antibodies revealed significant differences in antigenic specificity between the strains. Furthermore, a series of H3N2 isolates, derived using standard reassortment procedures, also showed differences in antigenic specificity in their haemagglutination-inhibition (HI) reactions with monoclonal antibodies after five passages in allantois-on-shell cultures. Variation between these isolates and their A/Victoria parent virus could be detected using SRH and hamster sera raised against each isolate. These results demonstrate variation between candidate influenza A virus vaccine strains, all possessing the same surface (H3N2) glycoproteins, expressed as a consequence of the reassortant system used for their production.