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

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.

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Publication Details

Journal
Journal of Clinical Investigation
Published
2025-04-03
DOI
https://doi.org/10.1172/jci186927
Citations
2
Primary Topic
HIV Research and Treatment
Type
article
Field-Weighted Citation Impact
2.07

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article

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

Zachary K. Sagawa, Amanda S. Woodward Davis, Glenda Gray, Asimenia Angelidou et al.
2 citations
Journal of Clinical Investigation
HIV Research and Treatment
2.07
article

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

Zachary K. Sagawa, Amanda S. Woodward Davis, Glenda Gray, Asimenia Angelidou, James G. Kublin, Avy Violari, Kinga K. Smolen, Nonhlanhla N. Mkhize, Georgia D. Tomaras, William O. Hahn, Catherine Yen, Holly Janes, Troy Martin, Barton F. Haynes, Kennedy Otwombe, Lawrence Corey, Ofer Levy, Margaret Brewinski Isaacs, Shi‐Yu Chen, Wilton B. Williams, Deirdre Josipovic, Laura Polakowski, Vuyelwa Baba
article en
2 citations

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.

Journal of Clinical InvestigationVol. 135(11)
National Health Laboratory Service (ZA), South African Medical Research Council (ZA), Boston Children's Hospital (US), Beth Israel Deaconess Medical Center (US), Infectious Disease Research Institute (US), Duke University (US), University of the Witwatersrand (ZA), University of Washington (US), Beth Israel Deaconess Hospital (US), Fred Hutch Cancer Center (US), Advanced Energy (United States) (US), Center for Human Genetics (US), Integrative Medicine Institute (US), National Institute of Allergy and Infectious Diseases (US), Perinatal HIV Research Unit (ZA)
Pfizer, GlaxoSmithKline, Sanofi, National Institutes of Health, National Institute of Allergy and Infectious Diseases
Good health and well-being
Openalex Percentile: Top 15%
HIV Research and Treatment
2.07
DOIOpen Access PDFOpenAlex
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