File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

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

TitleNext-generation T cell–activating vaccination increases influenza virus mutation prevalence
Authors
Issue Date2022
Citation
Science Advances, 2022, v. 8 n. 14 How to Cite?
AbstractTo 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.
Persistent Identifierhttp://hdl.handle.net/10722/314327

 

DC FieldValueLanguage
dc.contributor.authorBull, MB-
dc.contributor.authorGu, H-
dc.contributor.authorMa, NL-
dc.contributor.authorPerera, LIYANAGE P-
dc.contributor.authorPoon, LML-
dc.contributor.authorDoak, SAV-
dc.date.accessioned2022-07-18T06:15:59Z-
dc.date.available2022-07-18T06:15:59Z-
dc.date.issued2022-
dc.identifier.citationScience Advances, 2022, v. 8 n. 14-
dc.identifier.urihttp://hdl.handle.net/10722/314327-
dc.description.abstractTo 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.-
dc.languageeng-
dc.relation.ispartofScience Advances-
dc.titleNext-generation T cell–activating vaccination increases influenza virus mutation prevalence-
dc.typeArticle-
dc.identifier.emailGu, H: guhaogao@hku.hk-
dc.identifier.emailPoon, LML: llmpoon@hkucc.hku.hk-
dc.identifier.authorityPoon, LML=rp00484-
dc.identifier.authorityDoak, SAV=rp02141-
dc.identifier.doi10.1126/sciadv.abl5209-
dc.identifier.hkuros334270-
dc.identifier.volume8-
dc.identifier.issue14-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats