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

medRxiv : the preprint server for health sciences Pub Date : 2024-10-17 DOI:10.1101/2024.10.15.24315548

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, Troy M Martin, Bart Haynes, Wilton B Williams, Zachary K Sagawa, James Kublin, Laura Polakowski, Margaret Brewinski Isaacs, Catherine Yen, Georgia Tomaras, Lawrence Corey, Holly Janes, Glenda Gray

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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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新生儿 GLA-SE 佐剂 CH505TF gp120 HIV 疫苗 1 期随机试验的安全性和实施情况。

背景：新生儿免疫系统具有产生广泛中和抗体（bnAbs）的独特条件，因此婴儿是评估艾滋病毒候选疫苗的理想对象。我们介绍了一种新型葡萄糖吡喃糖基脂质 A（GLA）稳定乳液（SE）佐剂的设计和安全性，该佐剂掺入了旨在诱导针对 HIV 的 bnAbs 前体的婴儿初生 CH505 发射器创始者（CH505TF）gp120 免疫原。方法：HVTN 135 是一项关于 CH505TF+GLA-SE 或安慰剂的 I 期随机、安慰剂对照试验。在南非，年龄小于 5 天、母亲感染 HIV 但出生时 HIV 核酸阴性的健康婴儿在出生后 8 周、16 周、32 周和 54 周随机接受五次 CH505TF + GLA-SE 或安慰剂治疗：2020年11月至2022年1月，38名婴儿（中位年龄=4天；四分位距为4-4.75天）被纳入治疗。在被分配接受CH505TF + GLA-SE（安慰剂）的28名（10名）婴儿中，大多数（32/38）完成了5剂免疫系列和随访（35/38）。疫苗接种者（8 例，28.6% 局部反应；16 例，57.1% 全身反应）与安慰剂接种者（1 例，10% 局部反应，p = 0.25；4 例，40.0% 全身反应，p = 0.38）相比，诱发局部和全身反应的频率更高。除两例 2 级事件（疼痛、嗜睡）外，所有事件均为 1 级。未记录与疫苗相关的严重不良事件：这项研究表明，在接受标准婴儿疫苗接种的艾滋病毒暴露婴儿中开展新型艾滋病毒佐剂疫苗试验是可行的。CH505TF+GLA-SE疫苗的安全性令人放心：试验注册：ClinicalTrials.gov NCT04607408.Funding：摘要：本文概述了试验性 CH505TF 免疫原 + GLA-SE HIV 疫苗在感染 HIV 的母亲所生婴儿中的 1 期试验设计和安全性概况。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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