Goonetilleke Nilu P, McShane Helen, Hannan Carolyn M, Anderson Richard J, Brookes Roger H, Hill Adrian V S
Nuffield Department of Clinical Medicine, Oxford University, John Radcliffe Hospital, Oxford, United Kingdom.
J Immunol. 2003 Aug 1;171(3):1602-9. doi: 10.4049/jimmunol.171.3.1602.
Heterologous prime-boost immunization strategies can evoke powerful T cell immune responses and may be of value in developing an improved tuberculosis vaccine. We show that recombinant modified vaccinia virus Ankara, expressing Mycobacterium tuberculosis Ag 85A (M.85A), strongly boosts bacille Calmette-Guérin (BCG)-induced Ag 85A specific CD4(+) and CD8(+) T cell responses in mice. A comparison of intranasal (i.n.) and parenteral immunization of BCG showed that while both routes elicited comparable T cell responses in the spleen, only i.n. delivery elicited specific T cell responses in the lung lymph nodes, and these responses were further boosted by i.n. delivery of M.85A. Following aerosol challenge with M. tuberculosis, i.n. boosting of BCG with either BCG or M.85A afforded unprecedented levels of protection in both the lungs (2.5 log) and spleens (1.5 log) compared with naive controls. Protection in the lung correlated with the induction of Ag 85A-specific, IFN-gamma-secreting T cells in lung lymph nodes. These findings support further evaluation of mucosally targeted prime-boost vaccination approaches for tuberculosis.
异源初免-加强免疫策略可引发强大的T细胞免疫反应，在研发改进型结核病疫苗方面可能具有价值。我们发现，表达结核分枝杆菌Ag 85A（M.85A）的重组改良安卡拉痘苗病毒可显著增强卡介苗（BCG）诱导的小鼠Ag 85A特异性CD4(+)和CD8(+) T细胞反应。对BCG鼻内（i.n.）和肠胃外免疫的比较表明，虽然两种途径在脾脏中引发的T细胞反应相当，但只有鼻内接种在肺淋巴结中引发了特异性T细胞反应，并且这些反应通过鼻内接种M.85A得到进一步增强。在用结核分枝杆菌进行气溶胶攻击后，与未处理的对照相比，用BCG或M.85A对BCG进行鼻内加强免疫在肺部（2.5 log）和脾脏（1.5 log）均提供了前所未有的保护水平。肺部的保护作用与肺淋巴结中Ag 85A特异性、分泌IFN-γ的T细胞的诱导相关。这些发现支持对针对结核病的黏膜靶向初免-加强疫苗接种方法进行进一步评估。
