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

Mauro S. Malnati*, Silvia Heltai, Antonio Cosma, Peter Reitmeir, Simone Allgayer, Richard H. Glashoff, Walter Liebrich, Eftyhia Vardas, Nesrina Imami, Samantha Westrop, Silvia Nozza, Giuseppe Tambussi, Stefano Buttò, Emanuele Fanales-Belasio, Barbara Ensoli, Fabrizio Ensoli, Antonella Tripiciano, Claudio Fortis, Paolo Lusso, Guido PoliVolker Erfle, Harvey Holmes

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)46-56
Number of pages11
JournalJournal of Immunological Methods
Issue number1-2
Publication statusPublished - 31 Jan 2012
Externally publishedYes


  • ELISpot
  • HIV-1
  • Nef
  • Peptide
  • Tat
  • Vaccine


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