MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, United Kingdom.
J Virol. 2010 Aug;84(15):7815-21. doi: 10.1128/JVI.00726-10. Epub 2010 May 19.
Although major inroads into making antiretroviral therapy available in resource-poor countries have been made, there is an urgent need for an effective vaccine administered shortly after birth, which would protect infants from acquiring human immunodeficiency virus type 1 (HIV-1) through breast-feeding. Bacillus Calmette-Guérin (BCG) is given to most infants at birth, and its recombinant form could be used to prime HIV-1-specific responses for a later boost by heterologous vectors delivering the same HIV-1-derived immunogen. Here, two groups of neonate Indian rhesus macaques were immunized with either novel candidate vaccine BCG.HIVA(401) or its parental strain AERAS-401, followed by two doses of recombinant modified vaccinia virus Ankara MVA.HIVA. The HIVA immunogen is derived from African clade A HIV-1. All vaccines were safe, giving local reactions consistent with the expected response at the injection site. No systemic adverse events or gross abnormality was seen at necropsy. Both AERAS-401 and BCG.HIVA(401) induced high frequencies of BCG-specific IFN-gamma-secreting lymphocytes that declined over 23 weeks, but the latter failed to induce detectable HIV-1-specific IFN-gamma responses. MVA.HIVA elicited HIV-1-specific IFN-gamma responses in all eight animals, but, except for one animal, these responses were weak. The HIV-1-specific responses induced in infants were lower compared to historic data generated by the two HIVA vaccines in adult animals but similar to other recombinant poxviruses tested in this model. This is the first time these vaccines were tested in newborn monkeys. These results inform further infant vaccine development and provide comparative data for two human infant vaccine trials of MVA.HIVA.
尽管在资源匮乏的国家推广抗逆转录病毒疗法已经取得了重大进展，但仍迫切需要在婴儿出生后不久接种有效的疫苗，通过母乳喂养来保护婴儿免受人类免疫缺陷病毒 1 型（HIV-1）的感染。卡介苗（BCG）通常在婴儿出生时接种，其重组形式可用于启动 HIV-1 特异性反应，随后由异源载体传递相同的源自 HIV-1 的免疫原进行后续加强。在这里，两组新生印度猕猴分别用新型候选疫苗 BCG.HIVA(401)或其亲本菌株 AERAS-401 进行免疫接种，然后再用重组改良痘苗病毒安卡拉 MVA.HIVA 进行两剂免疫接种。HIVA 免疫原源自非洲 A 型 HIV-1。所有疫苗均安全，在注射部位引起的局部反应与预期反应一致。尸检时未发现任何全身不良反应或明显异常。AERAS-401 和 BCG.HIVA(401)都能诱导出高频率的 BCG 特异性 IFN-γ分泌淋巴细胞，但在 23 周内逐渐下降，但后者未能诱导出可检测到的 HIV-1 特异性 IFN-γ反应。MVA.HIVA 能在所有 8 只动物中引起 HIV-1 特异性 IFN-γ反应，但除了一只动物外，这些反应都很弱。与成人动物中两种 HIVA 疫苗产生的历史数据相比，婴儿中诱导的 HIV-1 特异性反应较低，但与该模型中测试的其他重组痘病毒相似。这是这些疫苗首次在新生猴子中进行测试。这些结果为进一步的婴儿疫苗开发提供了信息，并为 MVA.HIVA 的两项人类婴儿疫苗试验提供了比较数据。
