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

Avy Violari; Kennedy Otwombe; William Hahn; Shiyu Chen; Deirdre Josipovic; Vuyelwa Baba; Asimenia Angelidou; Kinga K Smolen; Ofer Levy; Nonhlanhla N Mkhize; Amanda S Woodward Davis; Troy M Martin; Barton F Haynes; Wilton B Williams; Zachary K Sagawa; James G Kublin; Laura Polakowski; Margaret Brewinski Isaacs; Catherine Yen; Georgia Tomaras; Lawrence Corey; Holly Janes; Glenda E Gray

doi:10.1172/JCI186927

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

J Clin Invest. 2025 Apr 3;135(11):e186927. doi: 10.1172/JCI186927. eCollection 2025 Jun 2.

Authors

Avy Violari¹, Kennedy Otwombe¹, William Hahn^{2

3}, Shiyu Chen², Deirdre Josipovic¹, Vuyelwa Baba⁴, Asimenia Angelidou⁵, Kinga K Smolen^{5

6}, Ofer Levy^{5

6}, Nonhlanhla N Mkhize^{7

8}, Amanda S Woodward Davis², Troy M Martin², Barton F Haynes⁹, Wilton B Williams¹⁰, Zachary K Sagawa¹¹, James G Kublin², Laura Polakowski¹², Margaret Brewinski Isaacs¹², Catherine Yen¹², Georgia Tomaras¹³, Lawrence Corey², Holly Janes², Glenda E Gray^{1

14}

Affiliations

¹ Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
² Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
³ Department of Allergy and Infectious Disease, Division of Medicine, University of Washington, Seattle, Washington, USA.
⁴ Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁵ Precision Vaccines Program, Boston Children's Hospital, Boston, Massachusetts, USA.
⁶ Harvard Medical School, Department of Neonatology, Beth Israel Medical Center, Boston, Massachusetts, USA.
⁷ National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
⁸ South African Medical Research Council Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁹ Department of Integrative Immunobiology, Duke Human Vaccine Institute; and.
¹⁰ Department of Surgery, Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
¹¹ Access to Advanced Health Institute, Seattle, Washington, USA.
¹² National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA.
¹³ Center for Human Systems Immunology, Departments of Surgery, Immunology, and Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA.
¹⁴ South African Medical Research Council, Cape Town, South Africa.

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.

Publication types

Clinical Trial, Phase I
Randomized Controlled Trial

MeSH terms

AIDS Vaccines* / administration & dosage
AIDS Vaccines* / adverse effects
AIDS Vaccines* / immunology
Adjuvants, Immunologic* / administration & dosage
Adjuvants, Immunologic* / adverse effects
Female
Glucosides
HIV Antibodies / immunology
HIV Envelope Protein gp120* / administration & dosage
HIV Envelope Protein gp120* / immunology
HIV Infections* / immunology
HIV Infections* / prevention & control
HIV-1* / immunology
Humans
Infant
Infant, Newborn
Lipid A* / administration & dosage
Lipid A* / adverse effects
Lipid A* / analogs & derivatives
Male

Substances

AIDS Vaccines
HIV Envelope Protein gp120
Adjuvants, Immunologic
Lipid A
glucopyranosyl lipid-A
HIV Antibodies
gp120 protein, Human immunodeficiency virus 1
Glucosides

Associated data

ClinicalTrials.gov/NCT04607408

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding