tetano
Editor, Senior Moderator
NPJ Vaccines
. 2022 Apr 11;7(1):42.
doi: 10.1038/s41541-022-00463-3.
Elimination of receptor binding by influenza hemagglutinin improves vaccine-induced immunity
Hilary E Hendin[SUP] 1 2 [/SUP], Pierre-Olivier Lavoie[SUP] 3 [/SUP], Jason M Gravett[SUP] 1 2 [/SUP], Stéphane Pillet[SUP] 2 3 [/SUP], Pooja Saxena[SUP] 3 [/SUP], Nathalie Landry[SUP] 3 [/SUP], Marc-André D'Aoust[SUP] 4 [/SUP], Brian J Ward[SUP] 5 6 [/SUP]
Affiliations
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[SUB]Y98F[/SUB]-VLP) and compared its immunogenicity and efficacy to a wild-type H1-VLP (H1[SUB]WT[/SUB]-VLP) in mice. The H1[SUB]Y98F[/SUB]-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[SUB]Y98F[/SUB]-VLP also resulted in a robust population of IL-2[SUP]+[/SUP]TNFα[SUP]+[/SUP]IFNγ[SUP]-[/SUP] CD4[SUP]+[/SUP] T cells that correlated with antibody responses. Compared to H1[SUB]WT[/SUB]-VLP vaccination, mice immunized with H1[SUB]Y98F[/SUB]-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.
. 2022 Apr 11;7(1):42.
doi: 10.1038/s41541-022-00463-3.
Elimination of receptor binding by influenza hemagglutinin improves vaccine-induced immunity
Hilary E Hendin[SUP] 1 2 [/SUP], Pierre-Olivier Lavoie[SUP] 3 [/SUP], Jason M Gravett[SUP] 1 2 [/SUP], Stéphane Pillet[SUP] 2 3 [/SUP], Pooja Saxena[SUP] 3 [/SUP], Nathalie Landry[SUP] 3 [/SUP], Marc-André D'Aoust[SUP] 4 [/SUP], Brian J Ward[SUP] 5 6 [/SUP]
Affiliations
- PMID: 35410323
- DOI: 10.1038/s41541-022-00463-3
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[SUB]Y98F[/SUB]-VLP) and compared its immunogenicity and efficacy to a wild-type H1-VLP (H1[SUB]WT[/SUB]-VLP) in mice. The H1[SUB]Y98F[/SUB]-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[SUB]Y98F[/SUB]-VLP also resulted in a robust population of IL-2[SUP]+[/SUP]TNFα[SUP]+[/SUP]IFNγ[SUP]-[/SUP] CD4[SUP]+[/SUP] T cells that correlated with antibody responses. Compared to H1[SUB]WT[/SUB]-VLP vaccination, mice immunized with H1[SUB]Y98F[/SUB]-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.