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Title:

A new antigen scanning strategy for monitoring HIV-1 specific T-cell immune responses.

Document type:
Journal Article; Research Support, Non-U.S. Gov't; Article
Author(s):
Malnati, MS; Heltai, S; Cosma, A; Reitmeir, P; Allgayer, S; Glashoff, RH; Liebrich, W; Vardas, E; Imami, N; Westrop, S; Nozza, S; Tambussi, G; Buttò, S; Fanales-Belasio, E; Ensoli, B; Ensoli, F; Tripiciano, A; Fortis, C; Lusso, P; Poli, G; Erfle, V; Holmes, H
Abstract:
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.
Journal title abbreviation:
J Immunol Methods
Year:
2012
Journal volume:
375
Journal issue:
1-2
Pages contribution:
46-56
Language:
eng
Fulltext / DOI:
doi:10.1016/j.jim.2011.09.005
Pubmed ID:
http://view.ncbi.nlm.nih.gov/pubmed/21963950
Print-ISSN:
0022-1759
TUM Institution:
Institut für Virologie
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