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

Laurel Yong Hwa Lee, Do Lien Anh Ha, Cameron Simmons, Menno D. De Jong, Nguyen Van Vinh Chau, Reto Schumacher, Chun Peng Yan, Andrew J. McMichael, Jeremy J. Farrar, Geoffrey L. Smith, Alain R.M. Townsend, Brigitte A. Askonas, Sarah Rowland-Jones, Tao Dong

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The threat of avian influenza A (H5N1) infection in humans remains a global health concern. Current influenza vaccines stimulate antibody responses against the surface glycoproteins but are ineffective against strains that have undergone significant antigenic variation. An alternative approach is to stimulate pre-existing memory T cells established by seasonal human influenza A infection that could cross-react with H5N1 by targeting highly conserved internal proteins. To determine how common cross-reactive T cells are, we performed a comprehensive ex vivo analysis of cross-reactive CD4+ and CD8+ memory T cell responses to overlapping peptides spanning the full proteome of influenza A/Viet Nam/CL26/2005 (H5N1) and influenza A/New York/232/2004 (H3N2) in healthy individuals from the United Kingdom and Viet Nam. Memory CD4+ and CD8+ T cells isolated from the majority of participants exhibited human influenza-specific responses and showed cross-recognition of at least one H5N1 internal protein. Participant CD4 + and CD8+ T cells recognized multiple synthesized influenza peptides, including peptides from the H5N1 strain. Matrix protein 1 (M1) and nucleoprotein (NP) were the immunodominant targets of cross-recognition. In addition, cross-reactive CD4+ and CD8 + T cells recognized target cells infected with recombinant vaccinia viruses expressing either H5N1 M1 or NP. Thus, vaccine formulas inducing heterosubtypic T cell-mediated immunity may confer broad protection against avian and human influenza A viruses.

Original languageEnglish
Pages (from-to)3478-3490
Number of pages13
JournalJournal of Clinical Investigation
Volume118
Issue number10
DOIs
Publication statusPublished - 1 Oct 2008

Cite this

Lee, Laurel Yong Hwa ; Ha, Do Lien Anh ; Simmons, Cameron ; De Jong, Menno D. ; Chau, Nguyen Van Vinh ; Schumacher, Reto ; Yan, Chun Peng ; McMichael, Andrew J. ; Farrar, Jeremy J. ; Smith, Geoffrey L. ; Townsend, Alain R.M. ; Askonas, Brigitte A. ; Rowland-Jones, Sarah ; Dong, Tao. / Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals. In: Journal of Clinical Investigation. 2008 ; Vol. 118, No. 10. pp. 3478-3490.
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title = "Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals",
abstract = "The threat of avian influenza A (H5N1) infection in humans remains a global health concern. Current influenza vaccines stimulate antibody responses against the surface glycoproteins but are ineffective against strains that have undergone significant antigenic variation. An alternative approach is to stimulate pre-existing memory T cells established by seasonal human influenza A infection that could cross-react with H5N1 by targeting highly conserved internal proteins. To determine how common cross-reactive T cells are, we performed a comprehensive ex vivo analysis of cross-reactive CD4+ and CD8+ memory T cell responses to overlapping peptides spanning the full proteome of influenza A/Viet Nam/CL26/2005 (H5N1) and influenza A/New York/232/2004 (H3N2) in healthy individuals from the United Kingdom and Viet Nam. Memory CD4+ and CD8+ T cells isolated from the majority of participants exhibited human influenza-specific responses and showed cross-recognition of at least one H5N1 internal protein. Participant CD4 + and CD8+ T cells recognized multiple synthesized influenza peptides, including peptides from the H5N1 strain. Matrix protein 1 (M1) and nucleoprotein (NP) were the immunodominant targets of cross-recognition. In addition, cross-reactive CD4+ and CD8 + T cells recognized target cells infected with recombinant vaccinia viruses expressing either H5N1 M1 or NP. Thus, vaccine formulas inducing heterosubtypic T cell-mediated immunity may confer broad protection against avian and human influenza A viruses.",
author = "Lee, {Laurel Yong Hwa} and Ha, {Do Lien Anh} and Cameron Simmons and {De Jong}, {Menno D.} and Chau, {Nguyen Van Vinh} and Reto Schumacher and Yan, {Chun Peng} and McMichael, {Andrew J.} and Farrar, {Jeremy J.} and Smith, {Geoffrey L.} and Townsend, {Alain R.M.} and Askonas, {Brigitte A.} and Sarah Rowland-Jones and Tao Dong",
year = "2008",
month = "10",
day = "1",
doi = "10.1172/JCI32460",
language = "English",
volume = "118",
pages = "3478--3490",
journal = "Journal of Clinical Investigation",
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Lee, LYH, Ha, DLA, Simmons, C, De Jong, MD, Chau, NVV, Schumacher, R, Yan, CP, McMichael, AJ, Farrar, JJ, Smith, GL, Townsend, ARM, Askonas, BA, Rowland-Jones, S & Dong, T 2008, 'Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals', Journal of Clinical Investigation, vol. 118, no. 10, pp. 3478-3490. https://doi.org/10.1172/JCI32460

Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals. / Lee, Laurel Yong Hwa; Ha, Do Lien Anh; Simmons, Cameron; De Jong, Menno D.; Chau, Nguyen Van Vinh; Schumacher, Reto; Yan, Chun Peng; McMichael, Andrew J.; Farrar, Jeremy J.; Smith, Geoffrey L.; Townsend, Alain R.M.; Askonas, Brigitte A.; Rowland-Jones, Sarah; Dong, Tao.

In: Journal of Clinical Investigation, Vol. 118, No. 10, 01.10.2008, p. 3478-3490.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals

AU - Lee, Laurel Yong Hwa

AU - Ha, Do Lien Anh

AU - Simmons, Cameron

AU - De Jong, Menno D.

AU - Chau, Nguyen Van Vinh

AU - Schumacher, Reto

AU - Yan, Chun Peng

AU - McMichael, Andrew J.

AU - Farrar, Jeremy J.

AU - Smith, Geoffrey L.

AU - Townsend, Alain R.M.

AU - Askonas, Brigitte A.

AU - Rowland-Jones, Sarah

AU - Dong, Tao

PY - 2008/10/1

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N2 - The threat of avian influenza A (H5N1) infection in humans remains a global health concern. Current influenza vaccines stimulate antibody responses against the surface glycoproteins but are ineffective against strains that have undergone significant antigenic variation. An alternative approach is to stimulate pre-existing memory T cells established by seasonal human influenza A infection that could cross-react with H5N1 by targeting highly conserved internal proteins. To determine how common cross-reactive T cells are, we performed a comprehensive ex vivo analysis of cross-reactive CD4+ and CD8+ memory T cell responses to overlapping peptides spanning the full proteome of influenza A/Viet Nam/CL26/2005 (H5N1) and influenza A/New York/232/2004 (H3N2) in healthy individuals from the United Kingdom and Viet Nam. Memory CD4+ and CD8+ T cells isolated from the majority of participants exhibited human influenza-specific responses and showed cross-recognition of at least one H5N1 internal protein. Participant CD4 + and CD8+ T cells recognized multiple synthesized influenza peptides, including peptides from the H5N1 strain. Matrix protein 1 (M1) and nucleoprotein (NP) were the immunodominant targets of cross-recognition. In addition, cross-reactive CD4+ and CD8 + T cells recognized target cells infected with recombinant vaccinia viruses expressing either H5N1 M1 or NP. Thus, vaccine formulas inducing heterosubtypic T cell-mediated immunity may confer broad protection against avian and human influenza A viruses.

AB - The threat of avian influenza A (H5N1) infection in humans remains a global health concern. Current influenza vaccines stimulate antibody responses against the surface glycoproteins but are ineffective against strains that have undergone significant antigenic variation. An alternative approach is to stimulate pre-existing memory T cells established by seasonal human influenza A infection that could cross-react with H5N1 by targeting highly conserved internal proteins. To determine how common cross-reactive T cells are, we performed a comprehensive ex vivo analysis of cross-reactive CD4+ and CD8+ memory T cell responses to overlapping peptides spanning the full proteome of influenza A/Viet Nam/CL26/2005 (H5N1) and influenza A/New York/232/2004 (H3N2) in healthy individuals from the United Kingdom and Viet Nam. Memory CD4+ and CD8+ T cells isolated from the majority of participants exhibited human influenza-specific responses and showed cross-recognition of at least one H5N1 internal protein. Participant CD4 + and CD8+ T cells recognized multiple synthesized influenza peptides, including peptides from the H5N1 strain. Matrix protein 1 (M1) and nucleoprotein (NP) were the immunodominant targets of cross-recognition. In addition, cross-reactive CD4+ and CD8 + T cells recognized target cells infected with recombinant vaccinia viruses expressing either H5N1 M1 or NP. Thus, vaccine formulas inducing heterosubtypic T cell-mediated immunity may confer broad protection against avian and human influenza A viruses.

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