Session 78Poster Presentations Therapeutic Vaccination Session Day and Time: Wednesday 1:30 - 3:30 pm Room: Hall A
646 Cross Recognition of HIV-specific CD8 Responses in Chronically HIV-1 Infected Patients Immunized by an HIV-1-LAI Recombinant Canarypox Vector (vCP1433) M. Le Garff*1, K. Gourlain1, R.Tubiana1, P. Haas1, C. Rabian2, T. Decoville1, C. Dalban1, M. Labalette 3, D. Olive4, V. Calvez1, P. Debre1, C. Katlama1, B. Autran 1, G. Carcelain1 1Pitié-Salpêtrière Hosp, Paris, France; 2St Louis Hosp, Paris, France; 3Univ Hosp, Lille, France; and 4Inst Paoli Calmettes, Marseille, France
Background: To evaluate the cross recognition of CD8+ responses generated in vivo against an HIV recombinant canarypox carrying HIV-1-LAI genes (env, gag, pol, and nef) and viral autologous strains in chronically HIV-1 infected patients (pts).
Methods: In a pilot, open, prospective, non-comparative vaccine trial (ANRS 094), 48 pts stable for at least 1 yr on HAART (CD4 > 400/ l, VL < 200 cp/ml) received 4 monthly injections (IM) of vCP1433. The pts p24 sequences were determined from intracellular proviral DNA before and after immunizations. Specific CD8+ T-cell responses were evaluated by IFNg ELISpot assay using 2 sets of HIV-LAI peptides: p24 HLA-restricted optimal peptides or 11 pools of 10 15-mers covering gag, or p24 HLA-restricted optimal peptides from autologous sequences.
Results: Using pools of LAI 15-mers, 14/19 (74%) pts displayed at baseline a specific CD8+ response with a median of 3/11 pools recognized. Overall a > 3-fold expansion of specific CD8+ cells was observed in 7/19 (37%) pts during the immunization phase and 2/19 pts developed new specific CD8+ responses. Using a median of 7 optimal p24 LAI peptides per pt, at baseline 4/6 pts had at least 1 positive response. During immunization, only 1/6 pts showed a > 3-fold expansion of specific CD8+ cells. P24 autologous sequences were stable before and after the immunization schedule in 5/6 pts: 4/6 pts had 1 (n = 1), 2 (n = 1) or 3 (n = 2) AA substitutions in CMH I-restricted epitopes between LAI and autologous sequences allowing us to test a median of 5.5 viral peptides per pt. Using optimal autologous peptides, at baseline 3/4 pts had at least 1 positive response and 2 of these 3 pts showed a > 3-fold expansion of autologous specific CD8+ responses during immunization: 1) 1 patient with cross recognition observed at baseline with no specific amplification during immunization; 2) 1 with amplification of the autologous specific CD8+, but no response against the LAI peptide; and 3) 1 with cross recognition observed at baseline and specific amplification during immunization.
Conclusions: HIV-1-LAI recombinant canarypox vCP1433 immunization can moderately amplify pre-existing memory cells and boost new specific CD8+ responses. Interestingly we observed 3 types of cross recognition between vaccine LAI and autologous virus sequences. Results are encouraging for future therapeutic HIV vaccine trials.
