Violari Avy, Otwombe Kennedy, Hahn William, Chen Shiyu, Josipovic Deirdre, Baba Vuyelwa, Angelidou Asimenia, Smolen Kinga K, Levy Ofer, Mkhize Nonhlanhla N, Woodward Davis Amanda S, Martin Troy M, Haynes Barton F, Williams Wilton B, Sagawa Zachary K, Kublin James G, Polakowski Laura, Brewinski Isaacs Margaret, Yen Catherine, Tomaras Georgia, Corey Lawrence, Janes Holly, Gray Glenda E
Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
J Clin Invest. 2025 Apr 3;135(11). doi: 10.1172/JCI186927. eCollection 2025 Jun 2.
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.
背景
新生儿免疫系统具有独特的能力来产生广泛中和抗体（bnAbs），因此婴儿是评估HIV疫苗候选物的理想对象。我们介绍了一种新的婴儿用吡喃葡萄糖基脂质A稳定乳液（GLA-SE）佐剂与一种首次用于婴儿的CH505传递者-奠基者（CH505TF）gp120免疫原混合的设计和安全性，该免疫原旨在诱导针对HIV的bnAbs前体。
方法
HIV疫苗试验网络135是一项I期随机、安慰剂对照试验，试验对象为CH505TF加GLA-SE或安慰剂。出生时年龄≤5天、母亲为HIV感染者但出生时HIV核酸阴性的健康婴儿，在出生时以及8、16、32和54周随机接受5剂CH505TF加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加GLA-SE的28名婴儿和分配接受安慰剂的10名婴儿中，大多数完成了5剂免疫接种系列（32/38）和随访（35/38）。与安慰剂接受者相比，疫苗接种者（8例，28.6%局部反应；16例，57.1%全身反应）的主动报告的局部和全身反应更频繁（1例，10%局部反应，P = 0.25；4例，40.0%全身反应，P = 0.38）。除2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。
结论
本研究说明了在接受标准婴儿疫苗接种的HIV暴露婴儿中进行新型婴儿佐剂HIV疫苗试验的可行性。CH505TF加GLA-SE疫苗的安全性令人放心。
试验注册
ClinicalTrials.gov NCT04607408。
资助
美国国立卫生研究院国家过敏和传染病研究所，资助号为UM1AI068614、UM1AI068635和UM1AI068618。
