Clinical and Immunologic Evaluation of Neuraminidase-Specific Influenza A Virus Vaccine in Humans

Groups of schoolchildren were immunized with an inactivated recombinant influenza virus vaccine specific for the neuraminidase antigen of Port Chalmers influenza A virus ($HeqlN2_{Ch}$), a conventional biphasic Port Chalmers strain of influenza virus vaccine ($H3_{Ch}N2_{Ch}$), or a placebo. Immunization with either virus vaccine was found to be safe and had no major adverse effects. Immunization with the$HeqlN2_{Ch}$vaccine resulted in no specific hemagglutination-inhibiting antibody response to$H3_{Ch}$antigen, although a specific neuraminidase antibody response to$N2_{Ch}$antigen was observed in >90% of the vaccinees. A subsequent natural outbreak of influenza virus resulted in serologically proven infection with$H3_{Ch}$virus in 26% of vaccinees receiving$H3_{Ch}N2_{Ch}$virus vaccine, 47% of those receiving$HeqlN2_{Ch}$virus vaccine, and 44% of those receiving a placebo. However, the protective efficacy against illness was 74.3% for the$H3_{Ch}N2_{Ch}$vaccine and only 51.4% for the$HeqlN2_{Ch}$vaccine. Regardless of the type of vaccine employed, vaccinees with serologic evidence of infection and clinical illness were found to have very low titers of hemagglutination-inhibiting and neuraminidase antibody. However, vaccinees with serologically proved infection but without clinical illness were found to have titers of antibody to neuraminidase before infection that were four-to eightfold higher than titers in vaccinees who were infected and who had clinical illness.