C1. Clinical trials (abstracts submitted to C1 should choose a secondary category that describes the subject matter of the trial)
Oral Abstract Submission
A primary challenge for HIV vaccine development is to raise antiviral antibodies capable of recognizing highly variable viral antigens. The full-length single chain (FLSC) gp120-CD4 chimeric protein was designed to present a highly conserved CD4-induced HIV-1 envelope structure that evokes cross-reactive humoral responses (Figure 1). IHV01 is a FLSC subunit vaccine formulated in alum adjuvant. The safety and immunogenicity of IHV01 was evaluated in this first-in-human phase 1a trial.
This randomized, double-blind placebo-controlled study involved three dose-escalating cohorts (75 µg, 150 µg, and 300 µg doses). Eligible participants were HIV-1 uninfected healthy volunteers aged 18 to 45 years. Participants in each cohort were block randomized in groups of four in a 3:1 ratio to receive either vaccine or placebo. Intramuscular injections were given on weeks 0, 4, 8, and 24. Participants were followed for an additional 24 weeks after the last immunization. Crossreactive antibody binding titers against diverse HIV envelopes and antigens and specific CD4i epitopes on gp120 were assessed.
Sixty five volunteers were enrolled– 49 vaccine and 16 placebo. Majority (81%) of vaccinations with IHV01 produced no localized or systemic reactions; no different from the control group. The overall incidence of adverse events (AEs) were not significantly different between groups. Majority (89%) of vaccine-related AEs were mild in severity. The most common vaccine-related AEs were injection site pain (31%), pruritus (10%), and headache (10%). There were no vaccine-related serious AE, discontinuation due to AE, or intercurrent HIV infection. By the final vaccination, all subjects in all cohorts had developed antibodies against IHV01; all placebo recipeints were negative. The antibodies induced by IHV01 reacted with envelope antigens from diverse HIV-1 strains (Figure 2).
IHV01 vaccine was safe, well tolerated, and immunogenic in all doses tested. The vaccine raised broadly reactive humoral responses against multiple gp120 domains, transition state structures, and CD4i epitopes.