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

Malnati M.S. ; Heltai S. ; Cosma A. ; Reitmeir P. ; Allgayer S. ; Glashoff R.H. ; Liebrich W. ; Vardas E. ; Imami N. ; Westrop S. ; Nozza S. ; Tambussi G. ; Butto S. ; Fanales-Belasio E. ; Ensoli B. ; Ensoli F. ; Tripiciano A. ; Fortis C. ; Lusso P. ; Poli G. ; Erfle V. ; Holmes H. (2012-01-18)

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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. © 2011 Elsevier B.V.

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