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

Ming Z M ZhengTiong Kit TanFernando Villalon-LetelierHilda LauYi-Mo DengSvenja FritzlarSophie A ValkenburgLeo L M PoonLeo L M PoonPatrick C ReadingAlain R TownsendLinda M Wakim
Published in: Science advances (2023)
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.
Keyphrases
  • respiratory tract
  • working memory
  • inflammatory response
  • sars cov
  • copy number
  • regulatory t cells
  • dna methylation
  • immune response
  • peripheral blood
  • toll like receptor
  • lps induced
  • dendritic cells
  • drug induced