A phase I trial in HIV negative healthy volunteers evaluating the effect of potent adjuvants on immunogenicity of a recombinant gp120 W61D derived from dual tropic R5X4 HIV-1 ACH320

Abstract

Thirty healthy HIV negative volunteers were randomised to receive 200 μg of rgp120 W61D in either: 3D-MPL and QS21, with an oil and water emulsion (SBAS-2) (13); or 3D-MPL and QS21 (SBAS-1) (11); or alum (six). Immunisations were given at 0, 4 and 28 weeks and 23 (77%) participants completed the schedule. Adverse events were more frequent ( P<0.001) and more severe ( P<0.001) in the SBAS-2 group. Binding antibodies to the homologous rgp120 W61D were detected after the first immunisation only in those receiving SBAS-1 and SBAS-2, were maximal after the third immunisation in all three groups, and persisted to week 84 only in the novel adjuvant groups. These differences were significant (p=0.02). Neutralising antibodies to TCLA-strains of HIV-1 were observed after the second immunisation in all three groups, were maximal after the third immunisation, but did not neutralise homologous or heterologous PBMC derived primary HIV-1 isolates. Proliferative T-cell responses to rgp120 W61D were maximal after the second immunisation and reached very high values in the SBAS-2 group. HIV-1 specific CD8 + MHC Class I restricted cytotoxic T-lymphocytes were not seen in a subset of participants tested at a single timepoint. SBAS-2 with rgp120 W61D induced antibody titres as high as those seen in HIV infection, but the quality of the antibodies remained different in that there was no evidence of primary isolate neutralisation. Although cell-mediated immunity was enhanced by SBAS-2 in terms of lymphoproliferative responses, HIV-1 specific CD8 + cytotoxicity was not demonstrated.