Augmentation of HIV-1-specific cytotoxic T lymphocytes and cellular immune responses in HIV-1 + individuals treated with a therapeutic vaccine plus antiretrovirals in a Phase II study: two year results.
Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrB539)
Fernandez-Cruz E, Munoz-Fernandez MA, Navarro J, Abad ML, Resino S, Jimenez JL, Canto C, Carbone J, Lopez F, Esteban M, M MF;;; EduardoFernandez-Cruz, Hospital General Universitario Gregorio Maranon, Division Immunology, C/ Doctor Esquerdo 46, Madrid 28007, Spain, Tel.: +34 91 586 84 23, Fax: +34 91 586 66 98, E-mail: efernandez@inmuno.hggm.es
We are currently testing a therapeutic vaccine (REMUNE), which is an inactivated gp120-depleted HIV-1 immunogen. A subset of 54 HIV+ subjects included in a multicenter, double-blind, adjuvant-controlled, randomized study of REMUNE versus Incomplete Freund's Adjuvant (IFA) coadministered with antiretrovirals was analyzed. An independent statistician identified patients in a closed-vault approach and produced the statistical results in a summary format. No cross summaries were undertaken to avoid the identification of treatment allocation. Subjects were inoculated with REMUNE/IFA every 3 months. Autologous B-EBV cells from each patient were infected with recombinant vaccinia viruses encoding HIVLAI Gag/pol, env (HIV-1 strain IIIB) and Lac (rVVTG) was used as control. At month 24, Gag/pol-specific memory CTL precursors are strongly increased in REMUNE group (n = 5) as compared to IFA group (n = 5) (mean CTLp: 4,427 ±454 cel/106 PBMC in REMUNE group vs 230 ± 57 cel/106 in IFA group). We observed an increase in env-specific memory CTL precursors (mean CTLp: 1,684 ± 1,298 cel/10E6 in REMUNE group vs 195 ± 41 cel/10E6 PBMC in IFA group). A significant increase of CD4 and CD8 memory T cells, with a concomitant decrease of CD45RA+CD62L+ was observed in REMUNE group (n = 14) as compared to IFA group (n = 13). Lymphocyte proliferation and IFN-g production to HIV-1 antigen-stimulated PBMCs increased significantly in REMUNE group (n = 27) as compared to IFA group (n = 27) (p = 0.049 and p = 0.002, respectively). Only the REMUNE group showed a good correlation between IFN-g and RANTES production (r = +0.87) (S), INF-g and MIP-1b (r = +0.72) (S), and RANTES and MIP 1b (r = +0.72) (S). No HIV-specific responses were observed pre-immunization in none of the groups. These results provide evidence that a therapeutic vaccine could provide a long-term induction of HIV-1 specific CTL and cellular immune responses.
Keywords: AEGIS, HIV-1, T-Lymphocytes, Cytotoxic, AIDS Vaccines, HIV Infections, HIV Seropositivity, RANTES, Antigens, CD4, Clinical Trials, Vaccination, Freund's Adjuvant, Immunization, remune, incomplete Freund's adjuvant, Human, immunology 000709
WeOrB539
