Development of a novel intranasal influenza vaccination strategy

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B916
Abstract ID: 4835

Presenting Author:
Miyu Moriyama , Postdoctoral Associate at Yale Sch. of Med., Howard Hughes Med. Inst.

Abstract:

Most currently approved seasonal influenza vaccines are administered intramuscularly. While parenteral vaccines are safe and induce systemic immunity, their efficacy varies depending on the matching of the vaccine seed virus strains and circulating viruses. One of the reasons why parenteral influenza vaccines are sensitive to the mismatch of the virus strains is because they induce very few T cells and mucosal IgA in the respiratory tract, which target conserved epitopes or are broadly reactive. To establish such protective mucosal immune responses, we have been developing an intranasal vaccine regimen which we named Prime and HA. In this approach, parenteral vaccination with mRNA-LNP first elicits systemic T and B cell responses (prime), followed by intranasal application of recombinant influenza HA proteins (HA). We observed a robust induction of HA-specific tissue-resident memory CD8⁺T cells, CD4⁺T cells, and IgA responses in the respiratory tract, in addition to local and systemic IgG responses. Notably, intranasal boosting with HA protein provided sterilizing immunity against lethal doses of viral challenge, which was not achieved by parenteral mRNA-LNP boosting. Our results demonstrated that intranasal application of unadjuvanted HA protein efficiently redirects circulating memory T and B cells into the respiratory mucosal sites and provides sterilizing immunity.