tetano
Editor, Senior Moderator
Virus Res
. 2022 Oct 24;198991.
doi: 10.1016/j.virusres.2022.198991. Online ahead of print.
Heterosubtypic immune pressure accelerates emergence of influenza A virus escape phenotypes in mice
Julie Ts Chu[SUP] 1 [/SUP], Haogao Gu[SUP] 1 [/SUP], Wanying Sun[SUP] 1 [/SUP], Rebecca Ly Fan[SUP] 1 [/SUP], John M Nicholls[SUP] 2 [/SUP], Sophie A Valkenburg[SUP] 3 [/SUP], Leo Lm Poon[SUP] 4 [/SUP]
Affiliations
Abstract
Rapid antigenic evolution of the influenza A virus surface antigen hemagglutinin undermines protection conferred by seasonal vaccines. Protective correlates targeted by universal vaccines such as cytotoxic T cells or HA stem directed broadly neutralizing antibodies have been shown to select for immune escape mutants during infection. We developed an in vivo serial passage mouse model for viral adaptation and used next generation sequencing to evaluate full genome viral evolution in the context of broadly protective immunity. Heterosubtypic immune pressure increased the incidence of genome-wide single nucleotide variants, though mutations found in early adapted populations were predominantly stochastic in nature. Prolonged adaptation under heterosubtypic immune selection resulted in the manifestation of highly virulent phenotypes that ablated vaccine mediated protection from mortality. High frequency mutations unique to escape phenotypes were identified within the polymerase encoding segments. These findings suggest that population-wide universal vaccine usage may drive formation of highly virulent escape variants attributed to polygenic changes.
Keywords: Heterosubtypic immunity; Influenza virus; Mouse-adaptation; Next-generation sequencing; Universal vaccines.
. 2022 Oct 24;198991.
doi: 10.1016/j.virusres.2022.198991. Online ahead of print.
Heterosubtypic immune pressure accelerates emergence of influenza A virus escape phenotypes in mice
Julie Ts Chu[SUP] 1 [/SUP], Haogao Gu[SUP] 1 [/SUP], Wanying Sun[SUP] 1 [/SUP], Rebecca Ly Fan[SUP] 1 [/SUP], John M Nicholls[SUP] 2 [/SUP], Sophie A Valkenburg[SUP] 3 [/SUP], Leo Lm Poon[SUP] 4 [/SUP]
Affiliations
- PMID: 36302472
- DOI: 10.1016/j.virusres.2022.198991
Abstract
Rapid antigenic evolution of the influenza A virus surface antigen hemagglutinin undermines protection conferred by seasonal vaccines. Protective correlates targeted by universal vaccines such as cytotoxic T cells or HA stem directed broadly neutralizing antibodies have been shown to select for immune escape mutants during infection. We developed an in vivo serial passage mouse model for viral adaptation and used next generation sequencing to evaluate full genome viral evolution in the context of broadly protective immunity. Heterosubtypic immune pressure increased the incidence of genome-wide single nucleotide variants, though mutations found in early adapted populations were predominantly stochastic in nature. Prolonged adaptation under heterosubtypic immune selection resulted in the manifestation of highly virulent phenotypes that ablated vaccine mediated protection from mortality. High frequency mutations unique to escape phenotypes were identified within the polymerase encoding segments. These findings suggest that population-wide universal vaccine usage may drive formation of highly virulent escape variants attributed to polygenic changes.
Keywords: Heterosubtypic immunity; Influenza virus; Mouse-adaptation; Next-generation sequencing; Universal vaccines.