Science Bite (3 minute oral presentation with PPT in live session with pre-recorded e-poster) - Students and ECR's only Lorne Infection and Immunity 2022

Single-cycle influenza virus vaccine generates lung CD8+ Trm with a diverse TCR repertoire that preclude the emergence of virus escape mutants (#70)

Ming Z. M. Zheng 1 , Fernando Villalon-Letelier 1 , Hilda Lau 2 , Svenja Fritzlar 1 , Yi-Mo Deng 2 , Tiong Tang 3 , Alain R. M. Townsend 3 , Patrick C. Reading 1 2 , Linda M. Wakim 1
  1. Department of Microbiology & Immunology , Peter Doherty Institute, Melbourne, VIC, Australia
  2. WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute, Melbourne, VIC, Australia
  3. MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, England, United Kingdom

Current influenza vaccines protect by evoking strain-specific neutralising antibodies, a form of immunity which leaves the population vulnerable to drifted seasonal and newly emerging pandemic strains. Developing vaccines that provide universal protection against both circulating and newly emerging influenza strains remains a health issue of utmost global importance. Vaccines that induce influenza reactive tissue-resident memory CD8+ T cells (Trm) along the respiratory tract have the potential to provide this coveted long term, cross strain immunity. Here, we tested the capacity of a single cycle candidate influenza vaccine (S-FLU) to evoke cross-reactive lung CD8+ Trm. We show that S-FLU immunisation of mice results in the deposition of influenza-specific lung CD8+ Trm which afforded protection against heterosubtypic infection. S-FLU vaccination induced lung CD8+ Trm of reduced antigen sensitivity compared to influenza specific CD8+ Trm generated following natural infection, and this was partly driven by an increased diversity within the T cell receptor (TCR) repertoire of S-FLU-generated CD8+ Trm. Interestingly, this diverse TCR repertoire within this S-FLU-generated memory T cell population, which was in part associated to the limited inflammatory profile evoked by this vaccination regime, was beneficial in thwarting the development of CD8+ T cell-mediated escape mutants. Our results show that S-FLU vaccination generates lung CD8+ Trm with broad TCR repertoire diversity, and this immune profile can protect against severe disease without driving the virus to rapidly evolve and escape vaccine-induced immunity.