Dose, Safety, Tolerability, and Immunogenicity of an HIV-1 Vaccine, VRC-HIVRGP096-00-VP, With Alum in Healthy Adults

Design: This is a Phase I, open-label, dose escalation study to evaluate the dose, safety, tolerability, and immunogenicity of VRC-HIVRGP096-00-VP (Trimer 4571) with aluminum hydroxide suspension (alum) as adjuvant in a three-injection regimen. The hypotheses were that the vaccine will be safe and tolerable and will induce detectable immune responses. The primary objective was to evaluate the safety and tolerability of the investigational vaccine at three doses administered with alum. Secondary objectives were to evaluate humoral and cellular immunogenicity of the investigational vaccine regimens. Study Product: VRC-HIVRGP096-00-VP (Trimer 4571) was developed by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID). The soluble HIV-1 envelope product consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505, with stabilizing mutations and engineered disulfide bonds, specifically recognized by broadly neutralizing antibodies and resists gp120 conformational change caused by CD4 binding. Injections were administered intramuscularly (IM) and subcutaneously (SC) in a 1 mL volume by needle and syringe. The product was provided at a 500 mcg/mL concentration in 3 mL glass vials filled to 1.2 +/- 0.10 mL. Adjuvant is an aluminum hydroxide suspension (alum) provided in a sterile, pyrogen-free suspension at a concentration of 5 mg/mL in 3 mL glass vials filled to 0.7 +/- 0.10 mL. Participants: Healthy adults ages 18 to 50. Study Plan: Participants received VRC-HIVRGP096-00-VP at doses of 100 mcg or 500 mcg, both with 500 mcg alum field mixed, administered via IM or SC injections. A dose escalation evaluation occurred to ensure the safety data supported proceeding to the higher dose. Participants were evaluated for safety and immune responses through blood collection at specified timepoints throughout the study. The study schema is below: \-------------------- Group 1: Participants = 3; Route = IM; Dose (mcg) = 100; Day\*\* 0, Week\*\* 8, Week\*\* 20 Group 2: Participants = 3; Route = SC; Dose (mcg) = 100; Day\*\* 0, Week\*\* 8, Week\*\* 20 Group 3: Participants = 5; Route = IM; Dose (mcg) = 500; Day\*\* 0, Week\*\* 8, Week\*\* 20 Group 4: Participants = 5; Route = SC; Dose (mcg) = 500; Day\*\* 0, Week\*\* 8, Week\*\* 20 Total = 16 Participants \*\*500 mcg of alum was mixed with Trimer 4571 for all groups Duration: Participants were followed for 40 weeks.