Differences in Magnitude, Breadth and Targets of HIV-Specific Response in Progressive versus Non-Progressive Acute/Early HIV Infection

GABRIELA TURK; YANINA GHIGLIONE; MARÍA EUGENIA SOCIAS; ANA MARÍA RODRIGUEZ; JULIANA FALIVENE; MARIA JULIA RUIZ; OMAR SUED ; DANIEL PRYLUKA; NATALIA LAUFER; PEDRO CAHN; HORACIO SALOMON; MARÍA MAGDALENA GHERARDI

Bangkok

Conferencia; AIDS Vaccine Conference 2011; 2011

Background: Characterizing HIV-specific immune response during acute infection and how it is modulated over time is highly relevant at HIV-vaccine design setting. Objective: To study HIV-specific T cell responses in Argentinean subjects (enrolled by the Argentinean Group of Seroconverters), during HIV seroconversion and up to the first year of infection. Methods:  Frozen PBMCs from 21 HIV+ seroconverters and 10 HIV+ elite controllers (EC) were used. Samples from seroconverters were obtained at enrollment (baseline), 3, 6 and 12 months post-infection. Seroconverters were classified as “Progressors” if CD4 count dropped below 350 cells/ml or experienced AIDS-related B/C events within the first year post-infection. HIV-specific T cell responses were evaluated by IFN-g ELISPOT. Magnitude, breadth and spot size (as indicator of released IFN-g) were compared inter- and intra-groups at baseline and follow-up samples, using parametric and non-parametric statistics. Results: Magnitude: Among seroconverters, Gag was preferentially targeted in “Non-Progressors” (NP) and Nef in “Progressors” (P). In EC, responses against Gag were predominantly found (Gag vs Nef and Env p<0.005). Within Gag, p24-specific cells dominated in NP and EC while p17 and p2-p7-p1-p6-specific cells dominated in P. Both at baseline and set-point samples, Gag-specific responses versus viral load and Nef-specific responses versus CD4 counts correlated significantly (inversely and directly, respectively). Breadth: Both at baseline (p=0.0115) and set-point samples (p=0.0428), P recognized fewer viral regions than EC. Spot size: NP and EC produced larger spots than P both when stimulating cells with HIV-specific peptides (p=0.0017 and p=0.0002, respectively) or CEF (CMV, Epstein Barr, Influenza)-specific peptides (p=0.02 and p=0.0039, respectively). This trend was maintained over time. Conclusions:  Early T cell responses (at baseline and set-point samples) preferentially targeting p24, higher breadth and larger spot size were associated with non-progressive acute/early infection indicating that these factors play an important role in early viral containment and should be considered for rational vaccine design.