A phase I clinical trial of a mufti-epitope polypeptide TAB9 combined withMontanide ISA 720 adjuvant in non-HIV-1 infected human volunteers

A phase I clinical trial was performed to examine the safety and immunogeni city of a mufti-epitope polypeptide comprising the central 15 amino acids o f the V3 loop from six HIV-1 isolates. This protein called TAB9 was emulsif ied in Montanide ISA720 (Seppic, Paris) and administered intramuscularly at doses of 0, 0.2 and 1 mg to 24 healthy, HIV-1 seronegative adult males. Th ree immunisations were given at months 0, 1 and 6 in a randomised, double b lind, placebo controlled clinical trial. The placebo was generally well tol erated. However, severe local reactions were observed in TAB9 vaccinated su bjects after the second and third inoculations. Seven out of eight voluntee rs from the lower dose group showed moderate or severe local inflammation, while four out of eight subjects from the higher dose group developed granu lomas and sterile abscesses. In general, the reactogenicity depended on the number of inoculations given and the dose of TAB9. Both doses were immunog enic, all immunised volunteers seroconverted and antibodies were broadly re active against the V3 peptides included in the protein. All vaccine's sera reacted against gp120 in Western blot and 50% of them also neutralised at l east one out of five laboratory isolates tested. No differences between dos es were found. Anti TAB9 lymphoproliferative responses were observed. being more intense in the high dose group. Due to the strong local reactions tha t were found in this study, a change in the formulation will be required fo r further trials with this vaccine candidate in humans. (C) 2001 Published by Elsevier Science Ltd.