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A new antigen scanning strategy for monitoring HIV-1 specific T-cell immune responses.
J. Immunol. Methods 375, 46-56 (2012)
Delineation of the immune correlates of protection in natural infection or after vaccination is a mandatory step for vaccine development. Although the most recent techniques allow a sensitive and specific detection of the cellular immune response, a consensus on the best strategy to assess their magnitude and breadth is yet to be reached. Within the AIDS Vaccine Integrated Project (AVIP http://www.avip-eu.org) we developed an antigen scanning strategy combining the empirical-based approach of overlapping peptides with a vast array of database information. This new system, termed Variable Overlapping Peptide Scanning Design (VOPSD), was used for preparing two peptide sets encompassing the candidate HIV-1 vaccine antigens Tat and Nef. Validation of the VOPSD strategy was obtained by direct comparison with 15mer or 20mer peptide sets in a trial involving six laboratories of the AVIP consortium. Cross-reactive background responses were measured in 80 HIV seronegative donors (HIV-), while sensitivity and magnitude of Tat and Nef-specific T-cell responses were assessed on 90 HIV+ individuals. In HIV-, VOPSD peptides generated background responses comparable with those of the standard sets. In HIV-1+ individuals the VOPSD pools showed a higher sensitivity in detecting individual responses (Tat VOPSD vs. Tat 15mers or 20mers: p≤0.01) as well as in generating stronger responses (Nef VOPSD vs. Nef 20mers: p<0.001) than standard sets, enhancing both CD4 and CD8 T-cell responses. Moreover, this peptide design allowed a marked reduction of the peptides number, representing a powerful tool for investigating novel HIV-1 candidate vaccine antigens in cohorts of HIV-seronegative and seropositive individuals.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Peptide; Tat; Nef; ELISpot; HIV-1; Vaccine
Language
english
Publication Year
2012
Prepublished in Year
2011
HGF-reported in Year
2011
ISSN (print) / ISBN
0022-1759
e-ISSN
1872-7905
Journal
Journal of Immunological Methods
Quellenangaben
Volume: 375,
Issue: 1-2,
Pages: 46-56
Publisher
Elsevier
Reviewing status
Peer reviewed
Institute(s)
Institute of Molecular Immunology (IMI)
Institute of Health Economics and Health Care Management (IGM)
Institute of Virology (VIRO)
Institute of Health Economics and Health Care Management (IGM)
Institute of Virology (VIRO)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30202 - Environmental Health
30202 - Environmental Health
Research field(s)
Immune Response and Infection
Genetics and Epidemiology
Genetics and Epidemiology
PSP Element(s)
G-501790-002
G-501790-001
G-501790-003
G-505300-002
G-501790-001
G-501790-003
G-505300-002
PubMed ID
21963950
Scopus ID
84855346712
Erfassungsdatum
2011-12-31