The binding of influenza hemagglutinin (HA) to sialic acid (SA) receptors plays a well-defined role in shaping infection but the impact of such binding on vaccine responses has not yet… Click to show full abstract
The binding of influenza hemagglutinin (HA) to sialic acid (SA) receptors plays a well-defined role in shaping infection but the impact of such binding on vaccine responses has not yet been explored. We generated a virus-like particle (VLP) vaccine bearing the HA of H1N1 A/California/07/09 that is unable to bind to its α(2,6)-linked SA receptor (H1 Y98F -VLP) and compared its immunogenicity and efficacy to a wild-type H1-VLP (H1 WT -VLP) in mice. The H1 Y98F -VLP elicited significantly stronger and more durable antibody responses (hemagglutination inhibition and microneutralization titers) and greater avidity maturation, likely attributable to improved germinal center formation. H1 Y98F -VLP also resulted in a robust population of IL-2 + TNFα + IFNγ − CD4 + T cells that correlated with antibody responses. Compared to H1 WT -VLP vaccination, mice immunized with H1 Y98F -VLP had 2.3-log lower lung viral loads and significantly lower pulmonary inflammatory cytokine levels 5 days post-challenge. These findings suggest that abrogation of HA-SA interactions may be a promising strategy to improve the quality and durability of influenza vaccine-induced humoral responses.
               
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