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Article: Next-generation T cell–activating vaccination increases influenza virus mutation prevalence
Title | Next-generation T cell–activating vaccination increases influenza virus mutation prevalence |
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Authors | |
Issue Date | 2022 |
Citation | Science Advances, 2022, v. 8 n. 14 How to Cite? |
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. |
Persistent Identifier | http://hdl.handle.net/10722/314327 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Bull, MB | - |
dc.contributor.author | Gu, H | - |
dc.contributor.author | Ma, NL | - |
dc.contributor.author | Perera, LIYANAGE P | - |
dc.contributor.author | Poon, LML | - |
dc.contributor.author | Doak, SAV | - |
dc.date.accessioned | 2022-07-18T06:15:59Z | - |
dc.date.available | 2022-07-18T06:15:59Z | - |
dc.date.issued | 2022 | - |
dc.identifier.citation | Science Advances, 2022, v. 8 n. 14 | - |
dc.identifier.uri | http://hdl.handle.net/10722/314327 | - |
dc.description.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. | - |
dc.language | eng | - |
dc.relation.ispartof | Science Advances | - |
dc.title | Next-generation T cell–activating vaccination increases influenza virus mutation prevalence | - |
dc.type | Article | - |
dc.identifier.email | Gu, H: guhaogao@hku.hk | - |
dc.identifier.email | Poon, LML: llmpoon@hkucc.hku.hk | - |
dc.identifier.authority | Poon, LML=rp00484 | - |
dc.identifier.authority | Doak, SAV=rp02141 | - |
dc.identifier.doi | 10.1126/sciadv.abl5209 | - |
dc.identifier.hkuros | 334270 | - |
dc.identifier.volume | 8 | - |
dc.identifier.issue | 14 | - |
dc.identifier.isi | WOS:000778897800019 | - |