Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals

Ly-H., Lee; Dla., Ha; Simmons, Cameron P.; Jong, de; Chau, Nguyen Vinh; Schumacher, Reto; Peng, Y C; McMichael, A J; Farrar, Jeremy; Smith, GJ; Townsend, Alain; Askonas, Brigitte A.; Rowland‐Jones, Sarah; Dong, Tuo

doi:10.1172/jci66865

Cited by 36 publications

(44 citation statements)

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“…peptides are conserved within H7N9, using IAVs that caused major human pandemics or epidemics as a reference (Table S1) (11,12) proteins, as identified in the Immune Epitope Database (www.immuneepitope.org). We found a substantial level of conservation within NP (Fig.…”

Section: Significancementioning

confidence: 99%

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

Quiñones-Parra

Grant

Loh

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

154

221

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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.

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Section: Significancementioning

confidence: 99%

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

Quiñones-Parra

Grant

Loh

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

154

221

View full text Add to dashboard Cite

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“…Since human T-cells specific for seasonal IAVs also display strong cross-reactivity with IAVs of other subtypes (Jameson et al, 1999;Kreijtz et al, 2008;Lee et al, 2008) and pH1N1 2009 viruses (Richards et al, 2010;Tu et al, 2010), it can be hypothesized that individuals with a history of IAV infection were protected from pH1N1 virus infections to a certain extent. This would imply that young children that are supposedly immunologically naïve for IAV would be more at risk for developing severe disease.…”

Section: T-cells Provide Protection Against Infection With Ph1n1mentioning

confidence: 99%

Cross-protective immunity against influenza pH1N1 2009 viruses induced by seasonal influenza A (H3N2) virus is mediated by virus-specific T-cells

Hillaire

Trierum

Kreijtz

et al. 2011

Journal of General Virology

113

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Influenza A (H1N1) viruses of swine origin were introduced into the human population in 2009 and caused a pandemic. The disease burden in the elderly was relatively low, which was attributed to the presence of cross-reacting serum antibodies in this age group, which were raised against seasonal influenza A (H1N1) viruses that circulated before 1957. It has also been described how infection with heterosubtypic influenza viruses can induce some degree of protection against infection by a novel strain of influenza virus. Here, we assess the extent of protective immunity against infection with the 2009 influenza A (H1N1) pandemic influenza virus that is afforded by infection with a seasonal influenza A (H3N2) virus in mice. Mice that experienced a primary A (H3N2) influenza virus infection displayed reduced weight loss after challenge infection and cleared the 2009 influenza A (H1N1) virus infection more rapidly. To elucidate the correlates of protection of this heterosubtypic immunity to pandemic H1N1 virus infection, adoptive transfer experiments were carried out by using selected post-infection lymphocyte populations. Virus-specific CD8+ T-cells in concert with CD4+ T-cells were responsible for the observed protection. These findings may not only provide an explanation for epidemiological differences in the incidence of severe pandemic H1N1 infections, they also indicate that the induction of cross-reactive virus-specific CD8+ and CD4+ T-cell responses may be a suitable approach for the development of universal influenza vaccines.

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“…Subsequently, antigen presenting cells (APC) migrate back to the draining lymph nodes to activate adaptive immune cells that are required for clearing IAV infection. The generation of antigen specific CD4 + and CD8 + cells are not only directly responsible for viral clearance, but are correlated with enhanced protection from IAV (2,10,14,20,21,40).…”

mentioning

confidence: 99%

Early Cytokine Dysregulation and Viral Replication Are Associated with Mortality During Lethal Influenza Infection

et al. 2014

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Infection with influenza A virus (IAV) leads to acute lung injury and possibly fatal complications, especially in immunocompromised, elderly, or chronically infected individuals. Therefore, it is important to study the factors that lead to pathology and mortality in infected hosts. In this report, we analyze immune responses to infection at a sublethal (0.1 LD 50 ) and lethal (1 LD 50 ) dose of the highly pathogenic IAV A/Puerto Rico/8/34 (PR8). Our experiments revealed that infection with a 1 LD 50 dose induced peak viral titers at day 2 compared to day 4 in the 0.1 LD 50 dose. Moreover, early cytokine dysregulation was observed in the lethal dose with significantly elevated levels of IFN-a, TNF-a, CXCL9, IL-6, and MCP-1 produced at day 2. Early inflammatory responses following infection with 1 LD 50 correlated with a greater influx of neutrophils into the lung. However, depletion of neutrophils enhanced morbidity following IAV infection. Though no differences in CD8 + cell function were observed, CD4 + effector responses were impaired in the lungs 8 days after infection with 1 LD 50 . Histological analysis revealed significant pathology in lethally infected mice at day 2 and day 6 postinfection, when viral titers remained high. Treating lethally infected mice with oseltamivir inhibited viral titers to sublethal levels, and abrogated the pathology associated with the lethal dose. Together, these results suggest that early cytokine dysregulation and viral replication play a role in pulmonary damage and high mortality in lethally infected mice.

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Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals

Cited by 36 publications

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

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

Cross-protective immunity against influenza pH1N1 2009 viruses induced by seasonal influenza A (H3N2) virus is mediated by virus-specific T-cells

Early Cytokine Dysregulation and Viral Replication Are Associated with Mortality During Lethal Influenza Infection

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Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals

Cited by 36 publications

References 0 publications

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

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

Cross-protective immunity against influenza pH1N1 2009 viruses induced by seasonal influenza A (H3N2) virus is mediated by virus-specific T-cells

Early Cytokine Dysregulation and Viral Replication Are Associated with Mortality During Lethal Influenza Infection

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

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