期刊
VACCINE
卷 32, 期 44, 页码 5801-5808出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2014.08.034
关键词
Modified vaccinia virus Ankara (MVA); Infant vaccine trial in Africa; Exposed-uninfected infants; HIV-1; Pediatric HIV-1 vaccines; KEPI vaccines; EPI vaccines
资金
- European and Developing Countries Clinical Trials Partnership (EDCTP) [CT.2006.33111.002]
- Bill and Melinda Gates Foundation
- Medical Research Council UK
- Swedish International Development Cooperation Agency (SIDA)
- NIAID of the National Institutes of Health [P30A1027757]
- NCI of the National Institutes of Health [P30A1027757]
- NIMH of the National Institutes of Health [P30A1027757]
- NIDA of the National Institutes of Health [P30A1027757]
- NICHD of the National Institutes of Health [P30A1027757]
- NHLBI of the National Institutes of Health [P30A1027757]
- NIA of the National Institutes of Health [P30A1027757]
- Medical Research Council [G1000800d] Funding Source: researchfish
Background: A safe, effective vaccine for breastfeeding infants born to HIV-1-positive mothers could complement antiretroviral therapy (ART) for prevention of mother-to-child transmission of HIV-1. To date, only a few HIV-1 vaccine candidates have been tested in infants. Trial design: A phase I/II randomized controlled trial PedVacc 002 was conducted to determine the safety and immunogenicity of a single, low dose of MVA.HIVA vaccine delivered intramuscularly to healthy 20-week-old infants born to HIV-1-positive mothers in Nairobi, Kenya. Methods: Pregnant HIV-1-positive women in the 2nd/3rd trimester of gestation were enrolled, provided with ART and self-selected their infant-feeding modality. Infants received nevirapine and cotrimoxazole prophylaxis. At 20 weeks of age, eligible HIV-1-negative infants were randomized to vaccine versus no-treatment arms and followed to 48 weeks of age for assessments of vaccine safety, HIV-1-specific T-cell responses and antibodies to routine childhood vaccines. Results: Between February and November 2010, 182 mothers were screened, 104 were eligible and followed on ART during pregnancy/postpartum, of whom 73 had eligible infants at 20 weeks postpartum. Thirty-six infants were randomized to vaccine and 37 to no treatment. Eighty-four percent of infants breastfed, and retention at 48 weeks was 99%. Adverse events were rare and similar between the two arms. HIV-1-specific T-cell frequencies in interferon-gamma ELISPOT assay were transiently higher in the MVA.HIVA arm (p = 0.002), but not above the threshold for a positive assay. Protective antibody levels were adequate and similar between arms for all routine childhood vaccines except HBV, where 71% of MVA.HIVA subjects compared to 92% of control subjects were protected (p = 0.05). Conclusions: This trial tested for the first time an MVA-vectored candidate HIV-1 vaccine in HIV-1-exposed infants in Africa, demonstrating trial feasibility and vaccine safety, low immunogenicity, and compatibility with routine childhood vaccinations. These results are reassuring for use of the MVA vector in more potent prime-boost regimens. (C) 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据