Phase I/II Study of a Candidate Vaccine Designed Against the B and E Subtypes of HIV-1

Abstract

A phase I/II trial of a candidate vaccine to prevent HIV infection was carried out in Bangkok, Thailand, testing AIDSVAX B/E (VaxGen, Inc., Brisbane, CA), a bivalent subunit vaccine prepared by combining recombinant gp120 from a subtype B virus (HIV-1MN) with gp120 from a subtype E virus (HIV-1A244) in alum adjuvant. The studies provide human data on the immunogenicity of various dose combination of non-subtype B vaccine antigens. The results suggest that AIDSVAX B/E is safe and immunogenic in humans. The optimal dose for humans in developing countries was 300 microg of each antigen (B and E). Clade E responses were measurably increased by immunizing with gp120 B/E over B alone. Using the B/E combination did not interfere with the response to either clade. Antibodies to AIDSVAX B/E were able to bind to oligomeric gp120 on the surface of cells infected with primary isolates of HIV-1.

HIV-1 Envelope Proteins and V1/V2 Domain Scaffolds with Mannose-5 to Improve the Magnitude and Quality of Protective Antibody Responses to HIV-1

“…A number of significant conclusions can be drawn from these studies. First, we found that gp120 from the A244 strain of HIV-1, included in the AIDSVAX B/E vaccine, and used in the RV144 trial (42,46,81), could be modified to bind multiple PG9-like antibodies with high affinity provided that the proper carbohydrate (mannose-5) was incorporated. Second, we found that fragments of A244 gp120 (e.g.…”

Randomized, Double‐Blind, Placebo‐Controlled Efficacy Trial of a Bivalent Recombinant Glycoprotein 120 HIV‐1 Vaccine among Injection Drug Users in Bangkok, Thailand

“…These assays were performed at the Thailand Ministry of Public Health (MOPH)-CDC Collaboration laboratory with EDTA-anticoagulated blood. At the VaxGen laboratory, 5 assays were used to measure rgp120 antibody responses: an ELISA for antibody that blocks the binding of A244 to the CD4 coreceptor; an ELISA for anti-A244 V2; an ELISA for anti-A244 V3; an ELISA for anti-gp120 MN/ A244 (mixed) binding antibodies; and an ELISA for MN neutralization [21,22]. Specimens collected at the last immunization visit before the first seropositive sample and 2 weeks after the last immunization visit were assayed for this purpose.…”

Clinical studies of experimental vaccines

“…The mechanisms responsible for the failure of this vaccine strategy include the high degree of envelope glycosylation which renders much of the surface of monomeric gp120 not accessible to antibodies [5,6 ], the CD4-and CCR5-binding sites being either poorly accessible (CD4) or absent in the absence of CD4 binding (CCR5) [5,6 ] and the high rate of HIV mutation associated with the generation of immune-escape virus mutants [7 ]. Monomeric gp120 has been extensively investigated in the clinical setting [8][9][10] and the protective effect of this vaccine strategy has been evaluated in two phase III efficacy trials in Thailand and the USA. Not surprisingly, these clinical trials have shown no protection against HIV infection [11,12].…”