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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/28543
Title: Conservation and diversity of influenza A H1N1 HLA-restricted T cell epitope candidates for epitope-based vaccines
Authors: Paul Thiamjoo Tan
A. T. Heiny
Olivo Miotto
Jerome Salmon
Ernesto T.A. Marques
Francois Lemonnier
J. Thomas August
Johns Hopkins University
Yong Loo Lin School of Medicine
University of Oxford
Mahidol University
University of Pittsburgh
Fundacao Oswaldo Cruz
Institut Pasteur, Paris
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology
Issue Date: 18-Jan-2010
Citation: PLoS ONE. Vol.5, No.1 (2010)
Abstract: Background: The immune-related evolution of influenza viruses is exceedingly complex and current vaccines against influenza must be reformulated for each influenza season because of the high degree of antigenic drift among circulating influenza strains. Delay in vaccine production is a serious problem in responding to a pandemic situation, such as that of the current H1N1 strain. Immune escape is generally attributed to reduced antibody recognition of the viral hemagglutinin and neuraminidase proteins whose rate of mutation is much greater than that of the internal non-structural proteins. As a possible alternative, vaccines directed at T cell epitope domains of internal influenza proteins, that are less susceptible to antigenic variation, have been investigated. Methodology/Principal Findings: HLA transgenic mouse strains expressing HLA class I A*0201, A*2402, and B*0702, and class II DRB1*1501, DRB1*0301 and DRB1*0401 were immunized with 196 influenza H1N1 peptides that contained residues of highly conserved proteome sequences of the human H1N1, H3N2, H1N2, H5N1, and avian influenza A strains. Fifty-four (54) peptides that elicited 63 HLA-restricted peptide-specific T cell epitope responses were identified by IFN-γ ELISpot assay. The 54 peptides were compared to the 2007-2009 human H1N1 sequences for selection of sequences in the design of a new candidate H1N1 vaccine, specifically targeted to highly-conserved HLA-restricted T cell epitopes. Conclusions/Significance: Seventeen (17) T cell epitopes in PB1, PB2, and M1 were selected as vaccine targets based on sequence conservation over the past 30 years, high functional avidity, non-identity to human peptides, clustered localization, and promiscuity to multiple HLA alleles. These candidate vaccine antigen sequences may be applicable to any avian or human influenza A virus. © 2010 Tan et al.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=77649294023&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/28543
ISSN: 19326203
Appears in Collections:Scopus 2006-2010

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