Anti-Neuraminidase Antibodies Reduce the Susceptibility to and Infectivity of Influenza A/H3N2 Virus.

Immune responses against neuraminidase (NA) are of great interest for developing more robust influenza vaccines, but the role of anti-NA antibodies on influenza infectivity has not been established. We conducted household transmission studies in Managua, Nicaragua to examine the impact of anti-NA antibodies on influenza A/H3N2 susceptibility and infectivity. Analyzing these data with mathematical models capturing household transmission dynamics and their drivers, we estimated that having higher preexisting antibody levels against the hemagglutinin (HA) head, HA stalk, and NA was associated with reduced susceptibility to infection (relative susceptibility 0.67, 95% Credible Interval [CrI] 0.50-0.92 for HA head; 0.59, 95% CrI 0.42-0.82 for HA stalk; and 0.56, 95% CrI 0.40-0.77 for NA). Only anti-NA antibodies were associated with reduced infectivity (relative infectivity 0.36, 95% CrI 0.23-0.55). These benefits from anti-NA immunity were observed even among individuals with preexisting anti-HA immunity. These results suggest that influenza vaccines designed to elicit NA immunity in addition to hemagglutinin immunity may not only contribute to protection against infection but reduce infectivity of vaccinated individuals upon infection.