TY - JOUR
T1 - A new antigen scanning strategy for monitoring HIV-1 specific T-cell immune responses
AU - Malnati, Mauro S.
AU - Heltai, Silvia
AU - Cosma, Antonio
AU - Reitmeir, Peter
AU - Allgayer, Simone
AU - Glashoff, Richard H.
AU - Liebrich, Walter
AU - Vardas, Eftyhia
AU - Imami, Nesrina
AU - Westrop, Samantha
AU - Nozza, Silvia
AU - Tambussi, Giuseppe
AU - Buttò, Stefano
AU - Fanales-Belasio, Emanuele
AU - Ensoli, Barbara
AU - Ensoli, Fabrizio
AU - Tripiciano, Antonella
AU - Fortis, Claudio
AU - Lusso, Paolo
AU - Poli, Guido
AU - Erfle, Volker
AU - Holmes, Harvey
PY - 2012/1/31
Y1 - 2012/1/31
N2 - 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.
AB - 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.
KW - ELISpot
KW - HIV-1
KW - Nef
KW - Peptide
KW - Tat
KW - Vaccine
UR - http://www.scopus.com/inward/record.url?scp=84855346712&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84855346712&partnerID=8YFLogxK
U2 - 10.1016/j.jim.2011.09.005
DO - 10.1016/j.jim.2011.09.005
M3 - Article
C2 - 21963950
AN - SCOPUS:84855346712
VL - 375
SP - 46
EP - 56
JO - Journal of Immunological Methods
JF - Journal of Immunological Methods
SN - 0022-1759
IS - 1-2
ER -