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[Preprint]. 2024 Oct 17:2024.10.15.24315548.

doi: 10.1101/2024.10.15.24315548.

Safety and implementation of a phase 1 randomized GLA-SE-adjuvanted CH505TF gp120 HIV vaccine trial in newborns

Avy Violari¹, Kennedy Otwombe¹, William Hahn², Shiyu Chen³, Deirdre Josipovic¹, Vuyelwa Baba⁴, Asimenia Angelidou⁵, Kinga K Smolen⁶, Ofer Levy⁷, Nonhlanhla N Mkhize⁸, Amanda S Woodward⁹, Troy M Martin³, Bart Haynes¹⁰, Wilton B Williams¹¹, Zachary K Sagawa¹², James Kublin¹³, Laura Polakowski¹⁴, Margaret Brewinski Isaacs¹⁵, Catherine Yen¹⁵, Georgia Tomaras¹⁶, Lawrence Corey¹⁷, Holly Janes¹⁷, Glenda Gray¹⁸

Affiliations

¹ Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
² Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, WA, USA; Department of Allergy and Infectious Disease, Division of Medicine, University of Washington, Seattle.
³ Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, WA, 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, MA, USA; Harvard Medical School; Boston, MA, USA; Department of Neonatology, Beth Israel Medical Center.
⁶ Precision Vaccines Program, Boston Children's Hospital; Boston, MA, USA; Harvard Medical School; Boston, MA, USA.
⁷ Precision Vaccines Program, Boston Children's Hospital; Boston, MA, USA; Harvard Medical School; Boston, MA, USA; Broad Institute of MIT & Harvard; Cambridge, MA, USA.
⁸ National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; SA MRC Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁹ Davis Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹⁰ Department of Integrative Immunobiology, Duke Human Vaccine Institute, Duke University School of Medicine, Durham NC 27710 USA.
¹¹ Department of Surgery, Human Vaccine Institute, Duke University School of Medicine; Durham, NC, USA.
¹² Access to Advanced Health Institute, Seattle, WA, USA.
¹³ Division of Vaccines and Infectious Diseases, Fred Hutch Cancer Center, Seattle, WA, USA.
¹⁴ National Institute of Allergy and Infectious Diseases, Rockville, MD, United States.
¹⁵ National Institute of Allergy and Infectious Diseases, Rockville, MD, USA.
¹⁶ Center for Human Systems Immunology, Departments of Surgery, Immunology, Molecular Genetics and Microbiology, Duke University, Durham, NC 27701, USA.
¹⁷ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹⁸ University of the Witwatersrand, Perinatal HIV Research Unit, Faculty of Health Sciences, Johannesburg, South Africa; South African Medical Research Council, Cape Town, South Africa.

PMID: 39484284
PMCID: PMC11527060
DOI: 10.1101/2024.10.15.24315548

Safety and implementation of a phase 1 randomized GLA-SE-adjuvanted CH505TF gp120 HIV vaccine trial in newborns

Avy Violari et al. medRxiv. 2024.

[Preprint]. 2024 Oct 17:2024.10.15.24315548.

doi: 10.1101/2024.10.15.24315548.

Authors

Affiliations

¹ Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
² Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, WA, USA; Department of Allergy and Infectious Disease, Division of Medicine, University of Washington, Seattle.
³ Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, WA, 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, MA, USA; Harvard Medical School; Boston, MA, USA; Department of Neonatology, Beth Israel Medical Center.
⁶ Precision Vaccines Program, Boston Children's Hospital; Boston, MA, USA; Harvard Medical School; Boston, MA, USA.
⁷ Precision Vaccines Program, Boston Children's Hospital; Boston, MA, USA; Harvard Medical School; Boston, MA, USA; Broad Institute of MIT & Harvard; Cambridge, MA, USA.
⁸ National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; SA MRC Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁹ Davis Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹⁰ Department of Integrative Immunobiology, Duke Human Vaccine Institute, Duke University School of Medicine, Durham NC 27710 USA.
¹¹ Department of Surgery, Human Vaccine Institute, Duke University School of Medicine; Durham, NC, USA.
¹² Access to Advanced Health Institute, Seattle, WA, USA.
¹³ Division of Vaccines and Infectious Diseases, Fred Hutch Cancer Center, Seattle, WA, USA.
¹⁴ National Institute of Allergy and Infectious Diseases, Rockville, MD, United States.
¹⁵ National Institute of Allergy and Infectious Diseases, Rockville, MD, USA.
¹⁶ Center for Human Systems Immunology, Departments of Surgery, Immunology, Molecular Genetics and Microbiology, Duke University, Durham, NC 27701, USA.
¹⁷ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
¹⁸ University of the Witwatersrand, Perinatal HIV Research Unit, Faculty of Health Sciences, Johannesburg, South Africa; South African Medical Research Council, Cape Town, South Africa.

PMID: 39484284
PMCID: PMC11527060
DOI: 10.1101/2024.10.15.24315548

Update in

Safety and implementation of phase I randomized GLA-SE-adjuvanted CH505TF gp120 HIV vaccine trial in newborns.
Violari A, Otwombe K, Hahn W, Chen S, Josipovic D, Baba V, Angelidou A, Smolen KK, Levy O, Mkhize NN, Woodward Davis AS, Martin TM, Haynes BF, Williams WB, Sagawa ZK, Kublin JG, Polakowski L, Brewinski Isaacs M, Yen C, Tomaras G, Corey L, Janes H, Gray GE. Violari A, et al. J Clin Invest. 2025 Apr 3;135(11):e186927. doi: 10.1172/JCI186927. eCollection 2025 Jun 2. J Clin Invest. 2025. PMID: 40178906 Free PMC article. Clinical Trial.

Abstract

Background: The 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 novel glucopyranosyl lipid A (GLA)-stable emulsion (SE) adjuvant admixed with a first-in-infant CH505 transmitter-founder (CH505TF) gp120 immunogen designed to induce precursors for bnAbs against HIV.

Methods: HVTN 135 is a phase I randomized, placebo-controlled trial of CH505TF+GLA-SE or placebo. Healthy infants in South Africa aged ≤5 days, born to mothers living with HIV but HIV nucleic acid negative at birth were randomized to five doses of CH505TF + GLA-SE or placebo at birth and 8, 16, 32, and 54 weeks.

Results: 38 infants (median age = 4 days; interquartile range 4, 4.75 days) were enrolled November 2020 to January 2022. Among 28 (10) infants assigned to receive CH505TF + GLA-SE (placebo), most (32/38) completed the 5-dose immunization series and follow-up (35/38). Solicited local and systemic reactions were more frequent in vaccine (8, 28.6% local; 16, 57.1% systemic) vs. placebo recipients (1, 10% local, p = 0.25; 4, 40.0% systemic, p = 0.38). All events were Grade 1 except two Grade 2 events (pain, lethargy). Serious vaccine-related adverse events were not recorded.

Conclusions: This study illustrates the feasibility of conducting trials of novel adjuvanted HIV vaccines in HIV-exposed infants receiving standard infant vaccinations. The safety profile of the CH505TF + GLA-SE vaccine was reassuring.

Trial registration: ClinicalTrials.gov NCT04607408.

Funding: National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH).

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Conflict of interest statement

Declaration of interests OL is a named inventor on patents relating to vaccine adjuvants and to human in vitro systems that model the safety and immunogenicity of adjuvants, vaccines and immunomodulators. He serves as a consultant to GSK and Hillevax and is a co-founder of Ovax, Inc. All other authors declare no conflict of interest.

Figures

**Figure 1.. CONSORT diagram.**
Flow of participants, from screening to randomization, enrolment, follow-up, and study completion.

**Figure 2.. 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 + 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 two different doses of CH505TF gp120 while keeping the same adjuvant dose.

**Figure 3.. Local and systemic reactogenicity.**
Percentage of participants who experienced each grade of local and systemic reactogenicity by arm.

See this image and copyright information in PMC

References

1. Fouda GG, et al. Immunological mechanisms of inducing HIV immunity in infants. Vaccine. 2020;38(3):411–415. - PMC - PubMed
1. Singh A, et al. AIDS Vaccine Research Subcommittee (AVRS) Consultation: Early-Life Immunization Strategies against HIV Acquisition. mSphere. 2019;4(4):e00320–19. - PMC - PubMed
1. Permar S, et al. Early Life HIV-1 Immunization: Providing a Window for Protection Before Sexual Debut. AIDS Res Hum Retroviruses. 2018;34(10):823–827. - PMC - PubMed
1. Corey L, et al. Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition. New Engl J Med. 2021;384(11):1003–1014. - PMC - PubMed
1. Baloh CH, et al. Biomarkers detected in cord blood predict vaccine responses in young infants. Front Immunol. 2023;14:1152538. - PMC - PubMed

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This is a preprint.

Safety and implementation of a phase 1 randomized GLA-SE-adjuvanted CH505TF gp120 HIV vaccine trial in newborns

Affiliations

Safety and implementation of a phase 1 randomized GLA-SE-adjuvanted CH505TF gp120 HIV vaccine trial in newborns

Authors

Affiliations

Update in

Abstract

Conflict of interest statement

Figures

References

Publication types

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical