AEGiS-13IAC: Low dose immunization using the adjuvant QS21 in combination with recombinant MN and/or bivalent MN/A244 (E type) gp120 in HIV-1 uninfected, low-risk volunteers (AVEG 036).

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Low dose immunization using the adjuvant QS21 in combination with recombinant MN and/or bivalent MN/A244 (E type) gp120 in HIV-1 uninfected, low-risk volunteers (AVEG 036).

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrC559)

Evans T, McElrath MJ, Gorse G, Mulligan M, Graham B, Schwartz D, Montefiori D, Francis D, Flores J
T. Evans, University of Rochester, 601 Elmwood Avenue, Box 689, Rochester, NY, 14642, United States, Tel.: +716-275-5871, Fax: +716-442-9328, E-mail: thomas_evans@urmc.rochester.edu

BACKGROUND: The saponin adjuvant QS21 has a dose-sparing effect in HIV-1 envelope immunization in HIV-uninfected human volunteers. However, the lowest immunogenic dose of gp120 used in combination with QS21 was not determined, and local reactogenicity was remarkable.

METHODS: A study was undertaken in 60 HIV-1 seronegative, low-risk volunteers using a QS21 (100 m g) formulation buffered with polysorbate 80 in combination with recombinant HIV-1 MN gp120, 3 m g or 0.5 m g (VaxGen), 6 m g bivalent MNgp120/A244 (Thai E), or placebo, administered on a 0, 1, 6 month schedule. Assessment of local pain, tenderness, and systemic signs or symptoms were performed after each immunization, and binding and neutralizing antibodies were measured two weeks after immunization.

RESULTS: The number of complaints of severe local pain and tenderness following any vaccination fell from 37% (7/19) in a previous low dose QS21 study to 10% (6/60) in this study. Binding Ab responses were measured to MN rgp120 and MN V3 loop were similar to those achieved historically with 300 m g of MN gp120. HIV-1 MN neutralization GMTs following the 2nd and 3rd immunizations were: 0.5 m g group (QS21 adjuvant) - 23 and 723, 3 m g (QS21 adjuvant)- 94 and 359, 3 m g (QS21 plus 6 m g alum ) - 206 and 383, bivalent MN/A244 (QS21 plus 12 m g alum) - 103 and 241. Placebo plus QS21 adjuvant - >10. Of note the highest 2 individual post third immunization titers (>3,000) achieved were in the lowest dose group (0.5 m g). No Env-specific CTL activity was detected using a chromium release assay.

CONCLUSIONS: This formulation of QS21 in polysorbate 80 appeared to reduce the number of severe local reactions, and allowed for a dose of 0.5 m g gp120 to be used with similar immunogenicity to that achieved with 100 to 600 m g in alum in previous studies. This adjuvant could markedly reduce cost, increase vaccine availability, and may allow for the development of candidate polyvalent HIV-1 gp120 subunits vaccines

Keywords: AEGIS, Immunization, Vaccination, Adjuvants, Immunologic, Saponins, Alum Compounds, HIV-1, HIV Infections, HIV Seropositivity, Polysorbates, QS 21, aluminum sulfate, Human, administration & dosage
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WeOrC559