Can Immunity Induced by the Human Influenza Virus N1 Neuraminidase Provide Some Protection from Avian Influenza H5N1 Viruses?

The infl uenza virus major surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) are the principal targets of the protective immune response. Licensed seasonal infl uenza virus vaccines are designed to elicit a protective immune response to the HA and NA proteins. However, only the concentration of HA protein is standardized in the currently approved inactivated seasonal infl uenza virus vaccines; the concentration of the NA protein is not. Hemagglutinin induces strain-specifi c neutralizing antibodies that prevent infection by antigenically related infl uenza viruses. Unlike HA-specifi c antibodies, NA-specifi c antibodies do not prevent infl uenza virus infection, and NA immunity is referred to as infection permissive [1]. However, humoral immunity induced by NA can markedly reduce virus replication and release, shortening the severity and duration of illness, a reasonable goal in the event of an infl uenza pandemic [2,3]. In mice, the induction of a relatively modest NA-specifi c humoral response is suffi cient to inhibit virus replication after challenge with homologous infl uenza virus [4–6]. NA-specifi c immunity in mice provides signifi cant cross-protection against replication of antigenically distinct viruses of the same subtype (drift variants) but not against different subtypes [7]. The degree of relatedness between the NA used for immunization and that of the challenge virus correlates well with the degree of cross-protection conferred by an NA-specifi c response. The emergence in 1968 of an H3N2 infl uenza virus with a novel HA subtype (H3) provided scientists with an opportunity to evaluate the role of NA-specifi c antibody in protection from infl uenza illness in humans. In a cohort of individuals with varying levels of N2-specifi c antibody, the severity of clinical illness correlated with the level of NA-specifi c serum antibody present at the time of virus challenge (H3N2) [3]. Ten of 11 men with serum NA inhibition antibody titers less than 1:4 presented with afebrile or febrile illness following virus challenge, while one displayed no clinical signs of illness. In contrast, four of ten men with serum NA inhibition antibody titers greater than 1:4 presented with illness, while six displayed no sign of illness. These data suggest that NA antibody can modify the severity of illness associated with infl uenza. However, even when the NA was fully conserved between the previously circulating H2N2 virus and the newly emerged H3N2 virus, and NA immunity may have blunted the severity of the pandemic, it was not suffi …