Safety and implementation of phase I randomized GLA-SE-adjuvanted CH505TF gp120 HIV vaccine trial in newborns

Abstract

BACKGROUNDThe neonatal immune system is uniquely poised to generate broadly neutralizing antibodies (bnAbs), and thus infants are ideal for evaluating HIV vaccine candidates. We present the design and safety of a new-in-infants glucopyranosyl lipid A-stable emulsion (GLA-SE) adjuvant admixed with a first-in-infant CH505 transmitter-founder (CH505TF) gp120 immunogen designed to induce precursors for bnAbs against HIV.METHODSHIV Vaccine Trials Network 135 is a phase I randomized, placebo-controlled trial of CH505TF plus GLA-SE or placebo. Healthy infants aged ≤5 days, born to mothers living with HIV but HIV nucleic acid-negative at birth, were randomized to 5 doses of CH505TF plus GLA-SE or placebo at birth and 8, 16, 32, and 54 weeks.RESULTSThirty-eight infants (median age 4 days; interquartile range 4-4.75 days) were enrolled November 2020 to January 2022. Among 28 infants assigned to receive CH505TF plus GLA-SE and 10 assigned to receive placebo, most completed the 5-dose immunization series (32/38) and follow-up (35/38). Solicited local and systemic reactions were more frequent in vaccine (8, 28.6% local; 16, 57.1% systemic) versus placebo recipients (1, 10% local, P = 0.25; 4, 40.0% systemic, P = 0.38). All events were grade 1 except 2 grade 2 events (pain, lethargy). Serious vaccine-related adverse events were not recorded.CONCLUSIONThis study illustrates the feasibility of conducting trials of new-in-infants adjuvanted HIV vaccines in HIV-exposed infants receiving standard infant vaccinations. The safety profile of the CH505TF plus GLA-SE vaccine was reassuring.TRIAL REGISTRATIONClinicalTrials.gov NCT04607408.FUNDINGNational Institute of Allergy and Infectious Diseases of the NIH under grants UM1AI068614, UM1AI068635, and UM1AI068618.

Keywords: AIDS vaccine; AIDS/HIV; Clinical Research; Vaccines.

Figure 1. Study design.

(A) Vaccine dosing schedule in relation to EPI vaccinations. (B) Study schema: Healthy infants without HIV born to mothers living with HIV were randomized to receive 5 doses of CH505TF gp120 plus GLA-SE vaccine or placebo, with the first dose within 5 days of birth. The 3-part design allowed for an initial assessment of safety in part A before the target adjuvant dose was studied in part B. Part C compared 2 different doses of CH505TF gp120 while keeping the same adjuvant dose.

Figure 2. CONSORT diagram.

Flow of participants, from screening to randomization, enrollment, follow-up, and study completion.

Figure 3. Local and systemic reactogenicity.

Percentage of participants who experienced each grade of local and systemic reactogenicity by arm.