Zhang Ming, Dong Chunsheng, Xiong Sidong
a Jiangsu Key Laboratory of Infection and Immunity , Institutes of Biology and Medical Sciences, Soochow University , Suzhou , P R China.
Hum Vaccin Immunother. 2017 Apr 3;13(4):816-822. doi: 10.1080/21645515.2016.1261229. Epub 2016 Dec 14.
Tuberculosis (TB) remains a major health problem worldwide, and the development of effective vaccines is urgently needed. Vaccination strategies based on heterologous prime-boost protocols using Mycobacterium bovis bacillus Calmette-Guérin (BCG) as primer and modified vaccinia virus Ankara strain expressing the mycobacterial antigen Ag85A (MVA85A) as booster may increase the protective efficacy of BCG. In addition, vaccination with the recombinant viral vaccine vesicular stomatitis virus (VSV)-846 (Rv3615c, Mtb10.4, and Rv2660c) can elicit a remarkable T-cell-mediated immune response and provide an effective long-term protection after the BCG challenge. In this study, we used VSV-846 to boost BCG and evaluated its immunogenicity in BALB/c mice. In this prime-boost approach, boosting with VSV-846 significantly enhanced IFN-γ CD4 T cell responses, which are crucial for anti-TB immune responses. Moreover, VSV-846 boosting significantly reduced pathology compared with mock vaccination, and decreased the bacterial loads in lung tissues compared with BCG or VSV-846 vaccination alone. The analysis of vaccine-induced immunity identified that polyfunctional T cells might contribute to the enhanced protection by VSV-846 boosting. This study proved that viral booster VSV-846 in mice improved the protection against mycobacteria infection, which could be helpful in designing an efficient vaccination strategy against TB in humans.
结核病（TB）仍是全球主要的健康问题，迫切需要开发有效的疫苗。基于异源初免-加强方案的疫苗接种策略，以卡介苗（BCG）作为初免，表达分枝杆菌抗原Ag85A的改良安卡拉痘苗病毒（MVA85A）作为加强免疫，可能会提高卡介苗的保护效力。此外，接种重组病毒疫苗水疱性口炎病毒（VSV）-846（Rv3615c、Mtb10.4和Rv2660c）可引发显著的T细胞介导的免疫反应，并在卡介苗激发后提供有效的长期保护。在本研究中，我们使用VSV-846加强卡介苗免疫，并评估其在BALB/c小鼠中的免疫原性。在这种初免-加强方法中，用VSV-846加强免疫显著增强了IFN-γ CD4 T细胞反应，这对抗结核免疫反应至关重要。此外，与假接种相比，VSV-846加强免疫显著减轻了病理变化，与单独接种卡介苗或VSV-846相比降低了肺组织中的细菌载量。对疫苗诱导免疫的分析表明，多功能T细胞可能有助于VSV-846加强免疫增强保护作用。本研究证明，小鼠中的病毒加强疫苗VSV-846提高了对分枝杆菌感染的保护作用，这可能有助于设计针对人类结核病的有效疫苗接种策略。
