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- W4223544304 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." @default.
- W4223544304 created "2022-04-15" @default.
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- W4223544304 date "2022-04-08" @default.
- W4223544304 modified "2023-10-13" @default.
- W4223544304 title "Next-generation T cell–activating vaccination increases influenza virus mutation prevalence" @default.
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- W4223544304 doi "https://doi.org/10.1126/sciadv.abl5209" @default.
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