Preexisting CD8 ⁺ T-cell immunity to the H7N9 influenza A virus varies across ethnicities

Abstract

Significance The severity of the novel H7N9 influenza A virus (IAV) and the lack of neutralizing antibodies raise real pandemic concerns. In this scenario, CD8 + T lymphocytes (CTLs) may provide a layer of protection against the H7N9 virus. Our study dissects the extent of preexisting CTL immunity with the potential to respond to H7N9. We identified conserved immunogenic peptides with the capacity to elicit robust CTL responses against any human IAV, including the H7N9 virus, as well as the mutations that abolish CTL recognition. The human leukocyte antigen class I molecules that present these peptides vary in prevalence depending on the ethnicity. Such analyses found that the Alaskan and Australian Indigenous people may be particularly vulnerable to the H7N9 influenza disease.

Influenza B virus-specific CD8+ T-lymphocytes strongly cross-react with viruses of the opposing influenza B lineage

“…The main function of CTLs is to detect and eliminate virus-infected cells, thereby restricting viral replication and accelerating viral clearance (Sridhar et al, 2013;van de Sandt et al, 2012 Lee et al, 2008;Quinones-Parra et al, 2014;van de Sandt et al, 2014a;Yewdell et al, 1985) and their contribution to cross-protective immunity has been demonstrated in various animal models (Flynn et al, 1998;Hillaire et al, 2011;Kreijtz et al, 2007Kreijtz et al, , 2009O'Neill et al, 2000;Weinfurter et al, 2011). Although in vivo evidence for the role of CTLs in protective heterosubtypic immunity in humans is limited (Epstein, 2006;McMichael et al, 1983;Slepushkin, 1959;Sridhar et al, 2013), several in vitro studies have demonstrated that human CTLs directed to seasonal influenza A viruses cross-react with possible pandemic influenza A viruses, including avian influenza viruses of the H5N1 and H7N9 subtype and swine origin vH3N2 viruses (Hillaire et al, 2013;Jameson et al, 1999;Kreijtz et al, 2008;Lee et al, 2008;Quinones-Parra et al, 2014;van de Sandt et al, 2014a). Virus-specific CTLs are also induced after influenza B virus infections (Robbins et al, 1989(Robbins et al, , 1995(Robbins et al, , 1997 …”

Influenza-Specific Antibody-Dependent Cellular Cytotoxicity: Toward a Universal Influenza Vaccine

“…CTLs targeting peptides from NP or M1 were shown to be effective in protecting from severe influenza infection (10)(11)(12)(13) and correlated with the reduction of symptomatic influenza disease in humans (13,14). Further, CTLs recognizing a broad range of influenza viruses are present in healthy human subjects (15,16). Conversely, Nabs directed to HA or NA can inhibit virus entry or prevent virus release from host cells, respectively (17,18).…”

Antigenic variability: Obstacles on the road to vaccines against traditionally difficult targets

“…Interestingly, it has been demonstrated that in the absence of preexisting neutralizing Abs indicating a lack of prior exposure, memory cytotoxic T lymphocytes (CTLs) specific for conserved epitopes of novel H7N9 influenza A virus were able to elicit strong CTL responses against any human influenza A virus. 28 However, specific HLA alleles expressed by certain ethnic groups (indigenous Australian and Alaskan populations) were associated with poor CTL responses to these conserved H7N9 peptides indicating additional problems for vaccine development. 28 Also, recent results highlight the need to design novel high-impact CTLinducing vaccines with greater capacity to suppress antigenic drift, since prior population immunity may reduce the expected impact of vaccines for pandemic influenza control.…”

“…28 However, specific HLA alleles expressed by certain ethnic groups (indigenous Australian and Alaskan populations) were associated with poor CTL responses to these conserved H7N9 peptides indicating additional problems for vaccine development. 28 Also, recent results highlight the need to design novel high-impact CTLinducing vaccines with greater capacity to suppress antigenic drift, since prior population immunity may reduce the expected impact of vaccines for pandemic influenza control. 29 Some successful preclinical studies offering novel strategies for influenza vaccine development are mentioned below.…”