Administration of IL-12 and GM-CSF in immunizations schemes delivering CRF12_BF Nef from DNA and MVA vectors enhanced both the magnitude and breadth of the immune response induced

ANA MARÍA RODRIGUEZ; MARÍA FERNANDA PASCUTTI; JULIANA FALIVENE; CYNTHIA MAETO; GABRIELA TURK; MM.GHERARDI

Buenos Aires

Congreso; 1 Congreso Fanco Argentino de Inmunologia; 2010

SAI-Francia

The Argentine HIV epidemic is characterized by the co-circulation of subtype B and BF variants. During the acute infection the majority of the HIV cellular immune response (CIR) is directed against Nef, placing it as a good candidate vaccine antigen. Here, we used it as a tool to study the impact of HIV-1 BF variants in the design of vaccines, since it is one of the most HIV variable proteins (difference B and BF: 24%). Previously, DNA and MVA vectors expressing NefBF were developed, finding a high specific response but with low cross-reactivity against NefB. The aim of this study was to analyze if the co-administration of molecular adjuvants, IL-12 and GM-CSF, could enhance the induced CIR generating higher levels of cross-reactivity. Mice received a prime, intramuscularly as follows: 3xDNAnefBF (Group I, GI), 3x DNAnefBF+DNA-IL-12 (GII), or DNA-GM-CSF (GIII), or both cytokine vectors (GIV). Afterwards all the groups were boosted with a dose of MVAnefBF intraperitoneally. Nine days after the last immunization, the specific CIR was evaluated in the spleen by ELISPOT using overlapping peptides comprising the full NefBF or B proteins. The highest response was detected in mice with both adjuvants (GIV, p