AIDSVAX^®(MN) in Bangkok Injecting Drug Users: A Report on Safety and Immunogenicity, Including Macrophage-Tropic Virus Neutralization

Abstract

A randomized, double-blind, placebo-controlled phase I/II study of AIDSVAX (MN) was conducted among injecting drug users in Bangkok, Thailand. Four doses of vaccine (300 microg of MN-rgp120 in alum) or placebo (alum) were given at study entry and at 1, 6, and 12 months. The objectives of the study were to evaluate (1) the feasibility of conducting vaccine trials in this population; (2) the safety of this candidate AIDS vaccine; and (3) the immunogenicity of this vaccine. Thirty-three volunteers (22 vaccine and 11 placebo recipients) were recruited. None were lost to follow-up during the 18-month study. Mild reactogenicity was noted, which was similar in both vaccine and placebo recipients. The vaccine induced anti-HIV-1 antibody in all vaccine recipients. Maximal titers of binding antibodies of MN-rgp120 and the V3 domain of MN-rgp120 were induced after the third (6 month) dose while maximal neutralizing antibodies followed the fourth (12 month) dose. The vaccine-induced antibodies from several volunteers were capable of neutralizing macrophage-tropic, subtype B viruses (301660 and JRCSF) detected in a PBMC-based assay. Binding and neutralizing antibodies declined about 10-fold in the 6 months after the last boost. Two vaccinees became infected during the trial, both with subtype E viruses. A phase III efficacy trial, using a bivalent gp120 vaccine containing antigens from a subtype B virus (MN) and a subtype E virus (A244), was initiated in March 1999 in injecting drug users in Bangkok.

HIV Vaccine efficacy trial: Glimmers of hope and the potential role of antibody-dependent cellular cytotoxicity

“…1C and in vaccine recipients. 25 However during the AIDSVAX TM B/E trial, blocking of HIV-1 A244 binding to CD4 and HIV-1 MN neutralization were not significantly different between the 106 HIV-1 infected and 115 randomly selected uninfected vaccine recipients. 23 The lack of efficacy of the AIDSVAX TM vaccines suggests that the breadth of the NAb responses elicited by this strategy was insufficient to protect against HIV-1 infection.…”

“…22,24 Robust binding antibody (Ab) titers were induced after the 3 rd (6 month) dose and high NAb titers (limited primarily to the vaccine strains and related viruses) were induced after the fourth (12 month) dose. 25,26 Both trials failed to protect subjects from HIV. Some reduction in HIV acquisition was observed among black and Asian volunteers although this was not statistically significant after adjusting for the subgroup analysis.…”

Safety and Immunogenicity of Combinations of Recombinant Subtype E and B Human Immunodeficiency Virus Type 1 Envelope Glycoprotein 120 Vaccines in Healthy Thai Adults

“…A number of HIV-1 envelope (gp120/gp160) vaccines have been tested in phase 1 and 2 trials in HIV-1-seronegative volunteers [10][11][12][13][14][15][16][17][18][19], and 2 subtype B gp120 subunit vaccines (MNand SF2-based) have been tested in Thailand [20,21]. The HIV gp120 subunit vaccines evaluated in human clinical trials in Thailand were derived from T cell line-adapted (TCLA) strains of HIV-1 that use the CXCR4 (X4) coreceptor.…”

Crosslinked HIV-1 envelope–CD4 receptor complexes elicit broadly cross-reactive neutralizing antibodies in rhesus macaques

“…The structural and antigenic characteristics of the free HIV envelope (Env) have been studied intensively in hopes of identifying a configuration that might serve as a subunit immunogen. However, these efforts have produced Env-based immunogens that typically fail to elicit antibodies capable of neutralizing more than a minor fraction of primary isolates (2)(3)(4)(5)(6)(7)(8)(9).…”