tetano
Editor, Senior Moderator
Sci Adv
. 2022 Apr 8;8(14):eabl5209.
doi: 10.1126/sciadv.abl5209. Epub 2022 Apr 6.
Next-generation T cell-activating vaccination increases influenza virus mutation prevalence
Maireid B Bull[SUP] 1 [/SUP], Haogao Gu[SUP] 2 [/SUP], Fionn N L Ma[SUP] 1 [/SUP], Liyanage P Perera[SUP] 3 [/SUP], Leo L M Poon[SUP] 1 2 [/SUP], Sophie A Valkenburg[SUP] 1 4 [/SUP]
Affiliations
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.
. 2022 Apr 8;8(14):eabl5209.
doi: 10.1126/sciadv.abl5209. Epub 2022 Apr 6.
Next-generation T cell-activating vaccination increases influenza virus mutation prevalence
Maireid B Bull[SUP] 1 [/SUP], Haogao Gu[SUP] 2 [/SUP], Fionn N L Ma[SUP] 1 [/SUP], Liyanage P Perera[SUP] 3 [/SUP], Leo L M Poon[SUP] 1 2 [/SUP], Sophie A Valkenburg[SUP] 1 4 [/SUP]
Affiliations
- PMID: 35385318
- DOI: 10.1126/sciadv.abl5209
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.