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NPJ Vaccines . Polyanhydride nanovaccine against H3N2 influenza A virus generates mucosal resident and systemic immunity promoting protection

tetano

Editor, Senior Moderator
NPJ Vaccines


. 2024 May 31;9(1):96.
doi: 10.1038/s41541-024-00883-3. Polyanhydride nanovaccine against H3N2 influenza A virus generates mucosal resident and systemic immunity promoting protection

Christopher E Lopez[SUP] 1 [/SUP], Zeb R Zacharias[SUP] 2 [/SUP], Kathleen A Ross[SUP] 3 [/SUP], Balaji Narasimhan[SUP] 3 4 [/SUP], Thomas J Waldschmidt[SUP] 2 3 [/SUP], Kevin L Legge[SUP] 5 6 7 [/SUP]



Affiliations
Abstract

Influenza A virus (IAV) causes significant morbidity and mortality worldwide due to seasonal epidemics and periodic pandemics. The antigenic drift/shift of IAV continually gives rise to new strains and subtypes, aiding IAV in circumventing previously established immunity. As a result, there has been substantial interest in developing a broadly protective IAV vaccine that induces, durable immunity against multiple IAVs. Previously, a polyanhydride nanoparticle-based vaccine or nanovaccine (IAV-nanovax) encapsulating H1N1 IAV antigens was reported, which induced pulmonary B and T cell immunity and resulted in cross-strain protection against IAV. A key feature of IAV-nanovax is its ability to easily incorporate diverse proteins/payloads, potentially increasing its ability to provide broad protection against IAV and/or other pathogens. Due to human susceptibility to both H1N1 and H3N2 IAV, several H3N2 nanovaccines were formulated herein with multiple IAV antigens to examine the "plug-and-play" nature of the polyanhydride nanovaccine platform and determine their ability to induce humoral and cellular immunity and broad-based protection similar to IAV-nanovax. The H3N2-based IAV nanovaccine formulations induced systemic and mucosal B cell responses which were associated with antigen-specific antibodies. Additionally, systemic and lung-tissue resident CD4 and CD8 T cell responses were enhanced post-vaccination. These immune responses corresponded with protection against both homologous and heterosubtypic IAV infection. Overall, these results demonstrate the plug-and-play nature of the polyanhydride nanovaccine platform and its ability to generate immunity and protection against IAV utilizing diverse antigenic payloads.


 
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