Potentiation of the immune response to influenza virus subunit vaccines

Influenza subunit vaccines are poorly immunogenic in unprimed lower animals and man and a method was sought to potentiate the humoral response. Intact heterologous influenza A virus vaccine (A/Victoria/3/75 [H3N2]) potentiated the antibody response of hamsters to A/NJ/76 [Hsw1 N1] subunit vaccines but large doses of intact virus were required. Studies in seronegative young human adults showed that much lower doses of homologous A/NJ/76 [Hsw1 N1] virus potentiated the antibody response to both the hemagglutinin and neuraminidase subunits of A/NJ/76 influenza vaccines. This suggests that future influenza subunit vaccines for use in seronegative people should contain a small amount of whole virus vaccine, sufficient to potentiate the immune response to the subunits but insufficient to be reactogenic.