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

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...

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Bibliographic Details
Published in:The Journal of clinical investigation 2008-10, Vol.118 (10), p.3478-3490
Main Authors: Lee, Laurel Yong-Hwa, Ha, Do Lien Anh, Simmons, Cameron, de Jong, Menno D, Chau, Nguyen Van Vinh, Schumacher, Reto, Peng, Yan Chun, McMichael, Andrew J, Farrar, Jeremy J, Smith, Geoffrey L, Townsend, Alain R M, Askonas, Brigitte A, Rowland-Jones, Sarah, Dong, Tao
Format: Article
Language:English
Subjects:
Adult
Analysis
Antibodies
Antigens
Avian flu
Avian influenza
Biomedical research
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Cell culture
Chemical properties
Cross Reactions - immunology
Disease transmission
Enzymes
Epitopes, T-Lymphocyte - immunology
Glycoproteins
Health
Health aspects
Humans
Immunologic Memory - immunology
Infections
Influenza A Virus, H3N2 Subtype - genetics
Influenza A Virus, H3N2 Subtype - immunology
Influenza A Virus, H5N1 Subtype - immunology
Influenza, Human - immunology
Influenza, Human - virology
Lymphocytes
Middle Aged
Nucleoproteins - immunology
Pandemics
Peptides
Physiological aspects
Proteins
Proteome
Risk factors
Seasons
T cells
T-Lymphocytes - immunology
United Kingdom
Vaccines
Vaccinia virus - genetics
Vaccinia virus - immunology
Vietnam
Viral Matrix Proteins - immunology
Viruses
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Description
Summary: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.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI32460