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)

Thirty healthy HIV negative volunteers were randomised to receive 200 mu g 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). Immunisatio ns 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(W 61D) were detected after the first immunisation only in those receiving SBA S-1 and SBAS-2, were maximal after the third immunisation in all three grou ps, and persisted to week 84 only in the novel adjuvant groups. These diffe rences 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 homologou s or heterologous PBMC derived primary HIV-1 isolates. Proliferative T-cell responses to rgp120(W61D) were maximal after the second immunisation and r eached very high values in the SBAS-2 group. HIV-1 specific CD8(+) MHC Clas s I restricted cytotoxic T-lymphocytes were not seen in a subset of partici pants tested at a single timepoint. SBAS-2 with rgp120(W61D) induced antibo dy titres as high as those seen in HIV infection, but the quality of the an tibodies remained different in that there was no evidence of primary isolat e neutralisation, Although cell-mediated immunity was enhanced by SBAS-2 in terms of lymphoproliferative responses, HIV-1 specific CD8(+) cytotoxicity was not demonstrated. (C) 2000 Elsevier Science Ltd. All rights reserved.