Nicol Mark Patrick, Grobler Liesl Anne
University of Cape Town, Institute of Infectious Diseases and Molecular Medicine, South Africa.
Curr Opin Mol Ther. 2010 Feb;12(1):124-34.
MVA-85A, in development by Oxford-Emergent Tuberculosis Consortium Ltd and the EU-funded research program TB-VAC, is a live attenuated viral vaccine expressing the immunodominant tuberculosis (TB) antigen 85A, and is intended for use in a heterologous prime-boost strategy to prevent TB. MVA-85A is highly immunogenic in both animals and humans, eliciting strong polyfunctional CD4+ T-cell responses when administered as a boost following BCG vaccination or when administered to individuals previously exposed to TB. Animal studies have demonstrated trends toward reduced pathology and bacillary burden for animals vaccinated with BCG prime followed by MVA-85A boost compared with BCG alone; however, these positive effects appear to be modest, and interpretation is limited by the small number of animals tested. The vaccine has an excellent safety profile in BCG-naïve, previously BCG-vaccinated and TB-exposed adults, as well as in BCG-vaccinated adolescents and children. At the time of publication, MVA-85A was in a more advanced stage of clinical development than other novel TB vaccine candidates, with a large-scale, proof-of-concept phase IIb clinical trial underway for the determination of safety, immunogenicity and prevention of TB in infants.
MVA - 85A由牛津 - 新兴结核病联盟有限公司和欧盟资助的研究项目TB - VAC研发,是一种表达免疫显性结核(TB)抗原85A的减毒活病毒疫苗,旨在用于异源初免 - 加强策略以预防结核病。MVA - 85A在动物和人类中均具有高度免疫原性,在卡介苗接种后作为加强剂给药时,或给予先前接触过结核病的个体时,可引发强烈的多功能CD4 + T细胞反应。动物研究表明,与单独使用卡介苗相比,先用卡介苗初免再用MVA - 85A加强免疫的动物,其病理变化和细菌负荷有减轻的趋势;然而,这些积极效果似乎并不显著,且由于测试动物数量较少,其解读受到限制。该疫苗在未接种卡介苗、先前接种过卡介苗以及接触过结核病的成年人中,以及在接种过卡介苗的青少年和儿童中,均具有良好的安全性。在发表之时,MVA - 85A处于比其他新型结核病疫苗候选物更先进的临床开发阶段,正在进行一项大规模的概念验证IIb期临床试验,以确定其在婴儿中的安全性、免疫原性和结核病预防效果。