一项针对新生儿的1期随机GLA-SE佐剂CH505TF gp120 HIV疫苗试验的安全性与实施情况

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

作者信息

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

机构信息

Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

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.

出版信息

medRxiv. 2024 Oct 17:2024.10.15.24315548. doi: 10.1101/2024.10.15.24315548.

DOI:10.1101/2024.10.15.24315548

PMID:39484284

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11527060/

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).

摘要

背景

新生儿免疫系统特别易于产生广泛中和抗体（bnAbs），因此婴儿是评估HIV疫苗候选物的理想对象。我们展示了一种新型吡喃葡萄糖基脂质A（GLA）稳定乳液（SE）佐剂与一种用于婴儿的首个CH505传播奠基者（CH505TF）gp120免疫原混合的设计及安全性，该免疫原旨在诱导针对HIV的bnAbs前体。

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。南非年龄≤5天、母亲为HIV感染者但出生时HIV核酸阴性的健康婴儿被随机分为在出生时以及8、16、32和54周接受五剂CH505TF + GLA - SE或安慰剂。

结果

2020年11月至2022年1月招募了38名婴儿（中位年龄 = 4天；四分位间距4, 4.75天）。在分配接受CH505TF + GLA - SE（安慰剂）的28（10）名婴儿中，大多数（32/38）完成了5剂免疫接种系列及随访（35/38）。与安慰剂接受者相比，疫苗接种者中 solicited局部和全身反应更频繁（8例，28.6%局部；16例，57.1%全身），而安慰剂接受者中分别为1例（10%局部，p = 0.25）；4例（40.0%全身，p = 0.38）。除两例2级事件（疼痛、嗜睡）外，所有事件均为1级。未记录到严重的疫苗相关不良事件。