Next-generation T cell–activating vaccination increases influenza virus mutation prevalence

Citations Over TimeTop 19% of 2022 papers

Abstract

To determine the potential for viral adaptation to T cell responses, we probed the full influenza virus genome by next-generation sequencing directly ex vivo from infected mice, in the context of an experimental T cell-based vaccine, an H5N1-based viral vectored vaccinia vaccine Wyeth/IL-15/5Flu, versus the current standard-of-care, seasonal inactivated influenza vaccine (IIV) and unvaccinated conditions. Wyeth/IL-15/5Flu vaccination was coincident with increased mutation incidence and frequency across the influenza genome; however, mutations were not enriched within T cell epitope regions, but high allele frequency mutations within conserved hemagglutinin stem regions and PB2 mammalian adaptive mutations arose. Depletion of CD4+ and CD8+ T cell subsets led to reduced frequency of mutants in vaccinated mice; therefore, vaccine-mediated T cell responses were important drivers of virus diversification. Our findings suggest that Wyeth/IL-15/5Flu does not generate T cell escape mutants but increases stochastic events for virus adaptation by stringent bottlenecks.

Related Papers

• → Rapid Semiautomated Subtyping of Influenza Virus Species during the 2009 Swine Origin Influenza A H1N1 Virus Epidemic in Milwaukee, Wisconsin(2009)39 cited
• → Production of a chimeric flavivirus that contains the major structural glycoprotein genes of T’Ho virus in the genetic background of Zika virus(2023)1 cited
• → Competitive virus assay method for titration of noncytopathogenic bovine viral diarrhea viruses (END+ and END− viruses)(2012)2 cited
• → The Virulence of West Nile Virus and TP 21 Virus and Their Application to a Group B Arbor Virus Vaccine(1961)15 cited
• → Murine Xenotropic Type C Viruses. IV. Replication and Pathogenesis in Ducks(1982)6 cited