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Published on: August 31, 2014
Safety and implementation of phase I randomized GLA-SE-adjuvanted CH505TF gp120 HIV vaccine trial in newborns
Avy Violari1, Kennedy Otwombe1, William Hahn2,3
1Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Insights
This study evaluated a new HIV vaccine in newborns, finding it safe and feasible for infants. The vaccine, CH505TF plus GLA-SE adjuvant, showed a reassuring safety profile in this early trial.
Area of Science:
- Immunology
- Vaccinology
- Neonatal Health
Background:
- Neonatal immune systems can generate broadly neutralizing antibodies (bnAbs), making infants ideal for HIV vaccine evaluation.
- Developing HIV vaccines for infants is crucial for preventing transmission and establishing long-term immunity.
Purpose of the Study:
- To assess the safety and feasibility of a novel, infant-specific HIV vaccine (CH505TF plus GLA-SE adjuvant) in healthy newborns.
- To evaluate the induction of antibody precursors for broadly neutralizing antibodies (bnAbs) against HIV in infants.
Main Methods:
- Phase I randomized, placebo-controlled trial (HVTN 135) involving healthy infants ≤5 days old.
- Infants received 5 doses of CH505TF plus GLA-SE adjuvant or placebo from birth through 54 weeks.
- Safety monitoring included solicited local/systemic reactions and adverse events.
Main Results:
- 38 infants enrolled; most completed the immunization series and follow-up.
- Solicited reactions were more frequent in the vaccine group but generally mild (Grade 1/2).
- No serious vaccine-related adverse events were reported, indicating a reassuring safety profile.
Conclusions:
- Conducting trials of adjuvanted HIV vaccines in HIV-exposed infants is feasible.
- The CH505TF plus GLA-SE vaccine demonstrated a favorable safety profile in newborns.
- This trial supports further investigation of infant HIV vaccine strategies.
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.
