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Sci Adv . Single-cycle influenza virus vaccine generates lung CD8+ Trm that cross-react against viral variants and subvert virus escape mutants

tetano

Editor, Senior Moderator
Sci Adv


. 2023 Sep 8;9(36):eadg3469.
doi: 10.1126/sciadv.adg3469. Epub 2023 Sep 8. Single-cycle influenza virus vaccine generates lung CD8[SUP]+[/SUP] Trm that cross-react against viral variants and subvert virus escape mutants

Ming Z M Zheng[SUP] 1 [/SUP], Tiong Kit Tan[SUP] 2 [/SUP], Fernando Villalon-Letelier[SUP] 1 [/SUP], Hilda Lau[SUP] 3 [/SUP], Yi-Mo Deng[SUP] 3 [/SUP], Svenja Fritzlar[SUP] 1 [/SUP], Sophie A Valkenburg[SUP] 1 4 [/SUP], Haogao Gu[SUP] 5 [/SUP], Leo L M Poon[SUP] 4 5 6 [/SUP], Patrick C Reading[SUP] 1 3 [/SUP], Alain R Townsend[SUP] 2 7 [/SUP], Linda M Wakim[SUP] 1 [/SUP]



Affiliations
Abstract

Influenza virus-specific tissue-resident memory (Trm) CD8[SUP]+[/SUP] T cells located along the respiratory tract provide cross-strain protection against a breadth of influenza viruses. We show that immunization with a single-cycle influenza virus vaccine candidate (S-FLU) results in the deposition of influenza virus nucleoprotein (NP)-specific CD8[SUP]+[/SUP] Trm along the respiratory tract that were more cross-reactive against viral variants and less likely to drive the development of cytotoxic T lymphocyte (CTL) escape mutants, as compared to the lung memory NP-specific CD8[SUP]+[/SUP] T cell pool established following influenza infection. This immune profile was linked to the limited inflammatory response evoked by S-FLU vaccination, which increased TCR repertoire diversity within the memory CD8[SUP]+[/SUP] T cell compartment. Cumulatively, this work shows that S-FLU vaccination evokes a clonally diverse, cross-reactive memory CD8[SUP]+[/SUP] T cell pool, which protects against severe disease without driving the virus to rapidly evolve and escape, and thus represents an attractive vaccine for use against rapidly mutating influenza viruses.


 
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