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

• Published in: Science advances Vol. 9; no. 36; p. eadg3469
• Main Authors: Zheng, Ming Z. M., Tan, Tiong Kit, Villalon-Letelier, Fernando, Lau, Hilda, Deng, Yi-Mo, Fritzlar, Svenja, Valkenburg, Sophie A., Gu, Haogao, Poon, Leo L. M., Reading, Patrick C., Townsend, Alain R., Wakim, Linda M.
• Format: Journal Article
• Language: English
• Published: American Association for the Advancement of Science 08-09-2023
• Subjects: Biomedicine and Life Sciences; Immunology; SciAdv r-articles; Virology
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.adg3469

Influenza virus–specific tissue-resident memory (Trm) CD8
+
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
+
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
+
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
+
T cell compartment. Cumulatively, this work shows that S-FLU vaccination evokes a clonally diverse, cross-reactive memory CD8
+
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.
S-FLU vaccine protects against the flu and discourages the emergence of viral escape variants.