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Sci Adv . Chimeric hemagglutinin split vaccines elicit broadly cross-reactive antibodies and protection against group 2 influenza viruses in mice

tetano

Editor, Senior Moderator
Sci Adv


. 2023 Sep 15;9(37):eadi4753.
doi: 10.1126/sciadv.adi4753. Epub 2023 Sep 13. Chimeric hemagglutinin split vaccines elicit broadly cross-reactive antibodies and protection against group 2 influenza viruses in mice

Eduard Puente-Massaguer[SUP] 1 [/SUP], Kirill Vasilev[SUP] 1 [/SUP], Annika Beyer[SUP] 1 [/SUP], Madhumathi Loganathan[SUP] 1 [/SUP], Benjamin Francis[SUP] 1 [/SUP], Michael J Scherm[SUP] 1 [/SUP], Guha Asthagiri Arunkumar[SUP] 1 [/SUP], Irene González-Domínguez[SUP] 1 [/SUP], Xueyong Zhu[SUP] 2 [/SUP], Ian A Wilson[SUP] 2 3 [/SUP], Lynda Coughlan[SUP] 4 5 [/SUP], Weina Sun[SUP] 1 [/SUP], Peter Palese[SUP] 1 6 [/SUP], Florian Krammer[SUP] 1 7 8 [/SUP]



Affiliations
Free PMC article Abstract

Seasonal influenza virus vaccines are effective when they are well matched to circulating strains. Because of antigenic drift/change in the immunodominant hemagglutinin (HA) head domain, annual vaccine reformulations are necessary to maintain a match with circulating strains. In addition, seasonal vaccines provide little to no protection against newly emerging pandemic strains. Sequential vaccination with chimeric HA (cHA) constructs has been proven to direct the immune response toward the immunosubdominant but more conserved HA stalk domain. In this study, we show that immunization with group 2 cHA split vaccines in combination with the CpG 1018 adjuvant elicits broadly cross-reactive antibodies against all group 2 HAs, as well as systemic and local antigen-specific T cell responses. Antibodies elicited after sequential vaccination are directed to conserved regions of the HA such as the stalk and the trimer interface and also to the N2 neuraminidase (NA). Immunized mice were fully protected from challenge with a broad panel of influenza A viruses.


 
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