HLA class I molecules consistently present internal influenza epitopes

Wahl, Angela; Schafer, Fredda; Bardet, Wilfried; Buchli, Rico; Air, Gillian M.; Hildebrand, William H.

doi:10.1073/pnas.0811271106

Cited by 58 publications

(46 citation statements)

References 43 publications

(50 reference statements)

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“…This profile has been established from both in vitro functional studies (6,24) and biochemical work with peptides eluted from IAV-infected cells on HPLC (25). However, the relative importance of different IAV epitopes is still far from clear when it comes to immunogenicity and protection.…”

Section: Discussionmentioning

confidence: 99%

Systematic identification of immunodominant CD8⁺T-cell responses to influenza A virus in HLA-A2 individuals

Zanker

Valkenburg

et al. 2011

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

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Immunodominant T-cell responses are important for virus clearance. However, the identification of immunodominant T-cell peptide + HLA glycoprotein epitopes has been hindered by the extent of HLA polymorphism and the limitations of predictive algorithms. A simple, systematic approach has been used here to screen for immunodominant CD8 + T-cell specificities. The analysis targeted healthy HLA-A2 + donors to allow comparison with responses to the well-studied influenza matrix protein 1 epitope. Although influenza matrix protein 1 was consistently detected in all individual samples in our study, the response to this epitope was only immunodominant in three of eight, whereas for the other five, prominent CD8 + T-cell responses tended to focus on various peptides from the influenza nucleoprotein that were not presented by HLA-A2. Importantly, with the four immunodominant T-cell epitopes identified here, only one would have been detected by the current prediction programs. The other three peptides would have been either considered too long or classified as not containing typical HLA binding motifs. Our data stress the importance of systematic analysis for discovering HLA-dependent, immunodominant CD8 + T-cell epitopes derived from viruses and tumors. Focusing on HLA-A2 and predictive algorithms may be too limiting as we seek to develop targeted immunotherapy and vaccine strategies that depend on T cell-mediated immunity.

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Section: Discussionmentioning

confidence: 99%

Systematic identification of immunodominant CD8⁺T-cell responses to influenza A virus in HLA-A2 individuals

Zanker

Valkenburg

et al. 2011

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

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“…We studied responses to influenza virus NP and M1. These proteins are conserved for both the H1N1 and H3N2 strains used for vaccination, and NP is a common target for CD8 T-cell immunity in both mice and humans (57,58). The majority of animals vaccinated with the recombinant influenza virus-SIV generated antiviral cytokine-producing CD8 and CD4 T cells in response to restimulation with overlapping peptides of NP (Fig.…”

Section: Influenza Virus-siv Vaccination Studies Of Macaquesmentioning

confidence: 99%

Evaluation of Recombinant Influenza Virus-Simian Immunodeficiency Virus Vaccines in Macaques

Sexton

Rose

Reece

et al. 2009

J Virol

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There is an urgent need for human immunodeficiency virus (HIV) vaccines that induce robust mucosal immunity. Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques. Influenza virus was readily detected from respiratory tract secretions, although the infections were asymptomatic. Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins. SIV-specific CD8 T-cell responses bearing the mucosal homing marker ␤7 integrin were induced by vaccination of naïve animals. Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection. Sequential vaccination with influenza virus-SIV recombinants of different subtypes (H1N1 followed by H3N2 or vice versa) produced only a limited boost in immunity, probably reflecting T-cell immunity to conserved internal proteins of influenza A virus. SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia. Although our results suggest that influenza virus-HIV vaccines hold promise for the induction of mucosal immunity to HIV, broader antigen cover will be needed to limit cytotoxic T-lymphocyte escape.

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“…Notably, there was amino acid divergence in position 473 in the nucleoprotein. Amino acid at position 473 (in the peptide of 473-481) in the nucleoprotein was relatively conserved in subtype H1N1 and H3N2 IAVs, and was reported to stimulate the host to produce IFN-c (Wahl et al, 2009). These findings are of interest because the non-coding regions and some coding regions of genome segments affect viral RNA synthesis and packing (Liang et al, 2005;Muster et al, 1991;Ng et al, 2008;Sun et al, 2015;Watanabe et al, 2003;Zheng et al, 1996).…”

Section: Evaluation Of Current Protocols For Using An Ai Multis-screementioning

confidence: 82%

Dynamics of virus shedding and antibody responses in influenza A virus-infected feral swine

Sun

Cunningham

Harris

et al. 2015

Journal of General Virology

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Given their free-ranging habits, feral swine could serve as reservoirs or spatially dynamic 'mixing vessels' for influenza A virus (IAV). To better understand virus shedding patterns and antibody response dynamics in the context of IAV surveillance amongst feral swine, we used IAV of feral swine origin to perform infection experiments. The virus was highly infectious and transmissible in feral swine, and virus shedding patterns and antibody response dynamics were similar to those in domestic swine. In the virus-inoculated and sentinel groups, virus shedding lasted #6 and #9 days, respectively. Antibody titres in inoculated swine peaked at 1 : 840 on day 11 post-inoculation (p.i.), remained there until 21 days p.i. and dropped to ,1 : 220 at 42 days p.i. Genomic sequencing identified changes in wildtype (WT) viruses and isolates from sentinel swine, most notably an amino acid divergence in nucleoprotein position 473. Using data from cell culture as a benchmark, sensitivity and specificity of a matrix gene-based quantitative reverse transcription-PCR method using nasal swab samples for detection of IAV in feral swine were 78.9 and 78.1 %, respectively. Using data from haemagglutination inhibition assays as a benchmark, sensitivity and specificity of an ELISA for detection of IAV-specific antibody were 95.4 and 95.0 %, respectively. Serological surveillance from 2009 to 2014 showed that ,7.58 % of feral swine in the USA were positive for IAV. Our findings confirm the susceptibility of IAV infection and the high transmission ability of IAV amongst feral swine, and also suggest the need for continued surveillance of IAVs in feral swine populations.

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HLA class I molecules consistently present internal influenza epitopes

Abstract: cytotoxic T lymphocyte ͉ major histocompatibility complex ͉ mass spectrometry

Cited by 58 publications

References 43 publications

Systematic identification of immunodominant CD8⁺T-cell responses to influenza A virus in HLA-A2 individuals

Systematic identification of immunodominant CD8⁺T-cell responses to influenza A virus in HLA-A2 individuals

Evaluation of Recombinant Influenza Virus-Simian Immunodeficiency Virus Vaccines in Macaques

Dynamics of virus shedding and antibody responses in influenza A virus-infected feral swine

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HLA class I molecules consistently present internal influenza epitopes

Abstract: cytotoxic T lymphocyte ͉ major histocompatibility complex ͉ mass spectrometry

Cited by 58 publications

References 43 publications

Systematic identification of immunodominant CD8+T-cell responses to influenza A virus in HLA-A2 individuals

Systematic identification of immunodominant CD8+T-cell responses to influenza A virus in HLA-A2 individuals

Evaluation of Recombinant Influenza Virus-Simian Immunodeficiency Virus Vaccines in Macaques

Dynamics of virus shedding and antibody responses in influenza A virus-infected feral swine

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Systematic identification of immunodominant CD8⁺T-cell responses to influenza A virus in HLA-A2 individuals

Systematic identification of immunodominant CD8⁺T-cell responses to influenza A virus in HLA-A2 individuals