新型 MVA85A 疫苗新生儿接种和有选择地延迟接种卡介苗用于人类免疫缺陷病毒感染母亲的婴儿：一项 2 期随机对照试验。
Safety and Immunogenicity of Newborn MVA85A Vaccination and Selective, Delayed Bacille Calmette-Guerin for Infants of Human Immunodeficiency Virus-Infected Mothers: A Phase 2 Randomized, Controlled Trial.
机构信息
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease & Molecular Medicine and Division of Immunology, Department of Science & Technology/National Research Foundation, University of Cape Town.
Desmond Tutu Tuberculosis Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences.
出版信息
Clin Infect Dis. 2018 Feb 1;66(4):554-563. doi: 10.1093/cid/cix834.
BACKGROUND
Vaccination of human immunodeficiency virus (HIV)-infected infants with bacille Calmette-Guérin (BCG) is contraindicated. HIV-exposed newborns need a new tuberculosis vaccination strategy that protects against tuberculosis early in life and avoids the potential risk of BCG disease until after HIV infection has been excluded.
METHODS
This double-blind, randomized, controlled trial compared newborn MVA85A prime vaccination (1 × 108 PFU) vs Candin® control, followed by selective, deferred BCG vaccination at age 8 weeks for HIV-uninfected infants and 12 months follow-up for safety and immunogenicity.
RESULTS
A total of 248 HIV-exposed infants were enrolled. More frequent mild-moderate reactogenicity events were seen after newborn MVA85A vaccination. However, no significant difference was observed in the rate of severe or serious adverse events, HIV acquisition (n = 1 per arm), or incident tuberculosis disease (n = 5 MVA85A; n = 3 control) compared to the control arm. MVA85A vaccination induced modest but significantly higher Ag85A-specific interferon gamma (IFNγ)+ CD4+ T cells compared to control at weeks 4 and 8 (P < .0001). BCG did not further boost this response in MVA85A vaccinees. The BCG-induced Ag85A-specific IFNγ+ CD4+ T-cell response at weeks 16 and 52 was of similar magnitude in the control arm compared to the MVA85A arm at all time points. Proliferative capacity, functional profiles, and memory phenotype of BCG-specific CD4 responses were similar across study arms.
CONCLUSIONS
MVA85A prime vaccination of HIV-exposed newborns was safe and induced an early modest antigen-specific immune response that did not interfere with, or enhance, immunogenicity of subsequent BCG vaccination. New protein-subunit and viral-vectored tuberculosis vaccine candidates should be tested in HIV-exposed newborns.
CLINICAL TRIALS REGISTRATION
NCT01650389.
背景
接种卡介苗（BCG）会对人类免疫缺陷病毒（HIV）感染的婴儿产生不良反应，故应禁止此类接种。HIV 暴露的新生儿需要一种新的结核病疫苗接种策略，该策略能在生命早期预防结核病，并且在排除 HIV 感染后，避免 BCG 疾病的潜在风险。
方法
本双盲、随机、对照试验比较了新生儿 MVA85A 初免（1×108PFU）与 Candin®对照的效果，随后对未感染 HIV 的婴儿选择性、延迟接种 BCG，并在 8 周龄和 12 个月龄时进行安全性和免疫原性随访。
结果
共纳入 248 名 HIV 暴露的婴儿。新生儿 MVA85A 接种后，更频繁地出现轻度至中度的反应原性事件。然而，与对照组相比，在严重或严重不良事件、HIV 感染（每组 1 例）或结核发病（MVA85A 组 5 例，对照组 3 例）的发生率方面，并无显著差异。与对照组相比，MVA85A 接种诱导了适度但显著更高的 Ag85A 特异性干扰素γ（IFNγ）+ CD4+T 细胞，在第 4 周和第 8 周时（P＜.0001）。BCG 并未进一步增强 MVA85A 疫苗接种者的这种反应。在所有时间点，与 MVA85A 组相比，对照组的 BCG 诱导的 Ag85A 特异性 IFNγ+ CD4+T 细胞反应在第 16 周和第 52 周时的幅度相似。BCG 特异性 CD4 反应的增殖能力、功能谱和记忆表型在各研究组之间相似。
结论
HIV 暴露新生儿接种 MVA85A 是安全的，并诱导了早期适度的抗原特异性免疫反应，该反应不会干扰或增强随后的 BCG 接种的免疫原性。新的蛋白亚单位和病毒载体结核候选疫苗应在 HIV 暴露的新生儿中进行测试。
临床试验注册
NCT01650389。
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