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Conservation and diversity of influenza A H1N1 HLA-restricted T cell epitope candidates for epitope-based vaccines

Tan, PT and Heiny, AT and Miotto, O and Salmon, J and Marques, ETA and Lemonnier, F and August, JT (2010) Conservation and diversity of influenza A H1N1 HLA-restricted T cell epitope candidates for epitope-based vaccines. PLoS ONE, 5 (1).

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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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Tan, PT
Heiny, AT
Miotto, O
Salmon, J
Marques, ETAmarques@pitt.eduMARQUES0000-0003-3826-9358
Lemonnier, F
August, JT
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorUnutmaz, DeryaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 18 January 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 1
DOI or Unique Handle: 10.1371/journal.pone.0008754
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Refereed: Yes
MeSH Headings: Amino Acid Sequence; Animals; Epitopes--chemistry; Epitopes--immunology; Humans; Influenza A Virus, H1N1 Subtype--immunology; Influenza Vaccines--immunology; Mice; Mice, Transgenic; Molecular Sequence Data; T-Lymphocytes--immunology
Other ID: NLM PMC2807450
PubMed Central ID: PMC2807450
PubMed ID: 20090904
Date Deposited: 31 Jul 2012 20:49
Last Modified: 10 Apr 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/13312

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