tetano
Editor, Senior Moderator
J Med Virol
. 2022 Feb 16.
doi: 10.1002/jmv.27662. Online ahead of print.
Evolutionary conservation and positive selection of Influenza A Nucleoprotein CTL epitopes for universal vaccination: a proof-of-concept
Michael C McGee[SUP] 1 [/SUP], Weishan Huang[SUP] 1 2 [/SUP]
Affiliations
Abstract
Influenza (flu) infection is a leading cause of respiratory disease and death worldwide. While seasonal flu vaccines are effective at reducing morbidity and mortality, such effects rely on the odds of successful prediction of the upcoming viral strains. Additional threats from emerging flu viruses that we cannot predict and avian flu viruses that can be directly transmitted to humans, urge the strategic development of universal vaccinations that can protect against flu viruses of different subtypes and across species. Annual flu vaccines elicit mainly humoral responses. Under circumstances when antibodies induced by vaccination fail to recognize and neutralize the emerging virus adequately, virus-specific cytotoxic T lymphocytes (CTLs) are the major contributors to the control of viral replication and elimination of infected cells. Our studies exploited the evolutionary conservation of influenza A nucleoprotein (NP) and the fact that NP-specific CTL responses pose a constant selecting pressure on functional CTL epitopes, to screen for NP epitopes that are highly conserved among heterosubtypes but are subjected to positive selection historically. We identified a region on NP that is evolutionarily conserved and historically positively selected (NP[SUB]137-182[/SUB] ) and validated that it contains an epitope that is functional in eliciting NP-specific CTL responses and immunity that can partially protect immunized mice against lethal dose infection of a heterosubtypic influenza A virus. Our proof-of-concept study supports the hypothesis that evolutionary conservation and positive selection of influenza nucleoprotein can be exploited to identify functional CTL epitope to elicit cross protection against different heterosubtypes, therefore, to help develop strategies to modify flu vaccine formula for a broader and more durable protective immunity. This article is protected by copyright. All rights reserved.
Keywords: CTL immunity; Influenza; conserved epitope; positive selection; universal vaccine.
. 2022 Feb 16.
doi: 10.1002/jmv.27662. Online ahead of print.
Evolutionary conservation and positive selection of Influenza A Nucleoprotein CTL epitopes for universal vaccination: a proof-of-concept
Michael C McGee[SUP] 1 [/SUP], Weishan Huang[SUP] 1 2 [/SUP]
Affiliations
- PMID: 35171514
- DOI: 10.1002/jmv.27662
Abstract
Influenza (flu) infection is a leading cause of respiratory disease and death worldwide. While seasonal flu vaccines are effective at reducing morbidity and mortality, such effects rely on the odds of successful prediction of the upcoming viral strains. Additional threats from emerging flu viruses that we cannot predict and avian flu viruses that can be directly transmitted to humans, urge the strategic development of universal vaccinations that can protect against flu viruses of different subtypes and across species. Annual flu vaccines elicit mainly humoral responses. Under circumstances when antibodies induced by vaccination fail to recognize and neutralize the emerging virus adequately, virus-specific cytotoxic T lymphocytes (CTLs) are the major contributors to the control of viral replication and elimination of infected cells. Our studies exploited the evolutionary conservation of influenza A nucleoprotein (NP) and the fact that NP-specific CTL responses pose a constant selecting pressure on functional CTL epitopes, to screen for NP epitopes that are highly conserved among heterosubtypes but are subjected to positive selection historically. We identified a region on NP that is evolutionarily conserved and historically positively selected (NP[SUB]137-182[/SUB] ) and validated that it contains an epitope that is functional in eliciting NP-specific CTL responses and immunity that can partially protect immunized mice against lethal dose infection of a heterosubtypic influenza A virus. Our proof-of-concept study supports the hypothesis that evolutionary conservation and positive selection of influenza nucleoprotein can be exploited to identify functional CTL epitope to elicit cross protection against different heterosubtypes, therefore, to help develop strategies to modify flu vaccine formula for a broader and more durable protective immunity. This article is protected by copyright. All rights reserved.
Keywords: CTL immunity; Influenza; conserved epitope; positive selection; universal vaccine.