Elimination of receptor binding by influenza hemagglutinin improves vaccine-induced immunity

Hilary E Hendin; Pierre-Olivier Lavoie; Jason M Gravett; Stéphane Pillet; Pooja Saxena; Nathalie Landry; Marc-André D'Aoust; Brian J Ward

doi:10.1038/s41541-022-00463-3

Elimination of receptor binding by influenza hemagglutinin improves vaccine-induced immunity

NPJ Vaccines. 2022 Apr 11;7(1):42. doi: 10.1038/s41541-022-00463-3.

Authors

Hilary E Hendin^{1

2}, Pierre-Olivier Lavoie³, Jason M Gravett^{1

2}, Stéphane Pillet^{2

3}, Pooja Saxena³, Nathalie Landry³, Marc-André D'Aoust⁴, Brian J Ward^{5

6}

Affiliations

¹ Department of Microbiology and Immunology, McGill University, 3775 University Street, Montréal, QC, H3A 2B4, Canada.
² Research Institute of McGill University Health Centre, Glen Site, 1001 Décarie Boul., Montréal, QC, H4AG 3J1, Canada.
³ Medicago Inc., 1020 Route de l'Église, Bureau 600, Québec, QC, Canada.
⁴ Medicago Inc., 1020 Route de l'Église, Bureau 600, Québec, QC, Canada. daoustma@medicago.com.
⁵ Research Institute of McGill University Health Centre, Glen Site, 1001 Décarie Boul., Montréal, QC, H4AG 3J1, Canada. brian.ward@mcgill.ca.
⁶ Medicago Inc., 1020 Route de l'Église, Bureau 600, Québec, QC, Canada. brian.ward@mcgill.ca.

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.