{"doi":"10.1101/2024.10.15.24315548","title":"Safety and implementation of a phase 1 randomized GLA-SE-adjuvanted CH505TF gp120 HIV vaccine trial in newborns","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).","journal":"medRxiv","year":2024,"id":489162,"datarank":0.2988114450118423,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.13401960171162589,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.13401960171162589,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":2,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT04607408"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":365988,"name":"Kennedy Otwombe","orcid":"0000-0002-7433-4383","position":1,"is_corresponding":false},{"id":788099,"name":"William O. 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Kublin","orcid":"0000-0003-1279-3741","position":15,"is_corresponding":false},{"id":331743,"name":"Laura Polakowski","orcid":"0000-0002-5476-7632","position":16,"is_corresponding":false},{"id":589610,"name":"Margaret Brewinski Isaacs","orcid":null,"position":17,"is_corresponding":false},{"id":343085,"name":"Catherine Yen","orcid":null,"position":18,"is_corresponding":false},{"id":258351,"name":"Georgia D. Tomaras","orcid":"0000-0001-8076-1931","position":19,"is_corresponding":false},{"id":96348,"name":"Lawrence Corey","orcid":"0000-0002-2179-2436","position":20,"is_corresponding":false},{"id":30696,"name":"Holly Janes","orcid":"0000-0002-3237-984X","position":21,"is_corresponding":false},{"id":355226,"name":"Glenda E. 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