Safety and immune responses after a 12-month booster in healthy HIV-uninfected adults in HVTN 100 in South Africa: A randomized double-blind placebo-controlled trial of ALVAC-HIV (vCP2438) and bivalent subtype C gp120/MF59 vaccines

Abstract

Background HVTN 100 evaluated the safety and immunogenicity of an HIV subtype C pox-protein vaccine regimen, investigating a 12-month booster to extend vaccine-induced immune responses. Methods and findings A phase 1-2 randomized double-blind placebo-controlled trial enrolled 252 participants (210 vaccine/42 placebo; median age 23 years; 43% female) between 9 February 2015 and 26 May 2015. Vaccine recipients received ALVAC-HIV (vCP2438) alone at months 0 and 1 and

Review of preventative HIV vaccine clinical trials in South Africa

“…After results were announced, the P5 (Pox-Protein Public Private Partnership) tailored the RV144 regimen to subtype C HIV strains. Adaptations of the RV144 vaccine regimen to South Africa included the use of the 96ZM651 gp120 env insert (subtype C) rather than the TH023 gp120 env insert (subtype E) used in RV144, inclusion of two subtype C gp120 Env proteins (TV1.C and 1086.C) in boost vaccinations (rather than subtype B and E proteins used in RV144), dose adjustments of the vector and protein, use of the MF59 instead of alum adjuvant, and the addition of boosters at month 12 and, in HVTN 702, month 18 [29]. The TV1.C and 1086.C gp120 Env proteins comprising bivalent subtype C gp120 were selected from candidate subtype C gp120 proteins according to an algorithm incorporating many factors.…”

“…Ad26 prime/Ad26+gp140 boost was the most immunogenic regimen, eliciting Env-specific binding antibody (100%), ADCP (80%) and T-cell responses (83%). 2015 [ 29 ] HVTN 100 (I-II) Subtype C ALVAC-HIV (vCP2438), a canarypox vector vaccine, at M0, 1, 3, 6, 12 and bivalent subtype C gp120/MF59, a protein vaccine, at M3, 6, 12 N = 252 low-risk adults, SA Generally safe, well-tolerated. Most produced IgG and T-cell responses.…”

Bringing the path toward an HIV-1 vaccine into focus

“…Nevertheless, models estimate that a vaccine with more than 50% efficacy for at least two years could significantly reduce the incidence of HIV-1 in high prevalence areas [5], so the modest efficacy of the immunization strategy used in the RV144 trial is an important benchmark that encourages cautious optimism that the path toward an HIV-1 vaccine is in view. The Uhambo trial tested in South Africa was a poxvirus prime, protein boost regimen like the RV144 vaccine regimen but with a different adjuvant, different envelope sequences [16,17] and additional gp120 protein boosting [18,19] with a goal of improving the breadth of immunity to subtype C and durability of vaccine-elicited antibody responses [20,21]. The Uhambo trial was recently stopped after an interim analysis found that the regimen did not prevent HIV-1 infection [7], highlighting the need for systems immunology studies to explain the different results of the two trials and better understand the balance of immunity needed to achieve protection in different populations.…”

Willingness to use HIV prevention methods among vaccine efficacy trial participants in Soweto, South Africa: discretion is important

“…The search for a preventative HIV vaccine continues. HVTN 702, a phase 2b/3 randomised, double-blind, placebo-controlled clinical trial, investigated the efficacy of ALVAC-HIV plus Bivalent Subtype C gp120/MF59 amongst at-risk HIV-uninfected young adults in South Africa [ 17 ]. In February 2020, HVTN 702 concluded that the vaccine regimen was not efficacious.…”