Stover C K, Bansal G P, Hanson M S, Burlein J E, Palaszynski S R, Young J F, Koenig S, Young D B, Sadziene A, Barbour A G
MedImmune, Inc., Gaithersburg, Maryland 20878.
J Exp Med. 1993 Jul 1;178(1):197-209. doi: 10.1084/jem.178.1.197.
The current vaccine against tuberculosis, Mycobacterium bovis strain bacille Calmette-Guerin (BCG), offers potential advantages as a live, innately immunogenic vaccine vehicle for the expression and delivery of protective recombinant antigens (Stover, C.K., V.F. de la Cruz, T.R. Fuerst, J.E. Burlein, L.A. Benson, L.T. Bennett, G.P. Bansal, J.F. Young, M.H. Lee, G.F. Hatfull et al. 1991. Nature [Lond]. 351:456; Jacobs, W.R., Jr., S.B. Snapper, L. Lugosi and B.R. Bloom. 1990. Curr. Top. Microbiol. Immunol. 155:153; Jacobs, W.R., M. Tuckman, and B.R. Bloom. 1987. Nature [Lond.]. 327:532); but as an attenuated intracellular bacterium residing in macrophages, BCG would seem to be best suited for eliciting cellular responses and not humoral responses. Since bacterial lipoproteins are often among the most immunogenic of bacterial antigens, we tested whether BCG expression of a target antigen as a membrane-associated lipoprotein could enhance the potential for a recombinant BCG vaccine to elicit high-titered protective antibody responses to target antigens. Immunization of mice with recombinant BCG vaccines expressing the outer surface protein A (OspA) antigen of Borrelia burgdorferi as a membrane-associated lipoprotein resulted in protective antibody responses that were 100-1,000-fold higher than responses elicited by immunization with recombinant BCG expressing OspA cytoplasmically or as a secreted fusion protein. Furthermore, these improved antibody responses were observed in heterogeneous mouse strains that vary in their immune responsiveness to OspA and sensitivity to BCG growth. Thus, expression of protective antigens as chimeric membrane-associated lipoproteins on recombinant BCG may result in the generation of new candidate vaccines against Lyme borreliosis and other human or veterinary diseases where humoral immunity is the protective response.
目前用于预防结核病的疫苗，即牛分枝杆菌卡介苗（BCG），作为一种活的、具有天然免疫原性的疫苗载体，在表达和递送保护性重组抗原方面具有潜在优势（斯托弗，C.K.，V.F. 德拉·克鲁兹，T.R. 富尔斯特，J.E. 伯林，L.A. 本森，L.T. 贝内特，G.P. 班萨尔，J.F. 杨，M.H. 李，G.F. 哈特富尔等，1991年，《自然》[伦敦]，351:456；雅各布斯，W.R.，Jr.，S.B. 斯纳珀，L. 卢戈西和B.R. 布鲁姆，1990年，《微生物学与免疫学当前专题》，155:153；雅各布斯，W.R.，M. 塔克曼和B.R. 布鲁姆，1987年，《自然》[伦敦]，327:532）；但作为一种驻留在巨噬细胞内的减毒细菌，BCG似乎最适合引发细胞免疫反应而非体液免疫反应。由于细菌脂蛋白通常是细菌抗原中免疫原性最强的，我们测试了将目标抗原作为膜相关脂蛋白在BCG中表达是否能增强重组BCG疫苗引发针对目标抗原的高滴度保护性抗体反应的潜力。用表达伯氏疏螺旋体外表面蛋白A（OspA）抗原作为膜相关脂蛋白的重组BCG疫苗免疫小鼠，所引发的保护性抗体反应比用在细胞质中表达OspA或作为分泌融合蛋白表达OspA的重组BCG免疫所引发的反应高100 - 1000倍。此外，在对OspA的免疫反应性和对BCG生长的敏感性各不相同的异种小鼠品系中也观察到了这些改善的抗体反应。因此，在重组BCG上作为嵌合膜相关脂蛋白表达保护性抗原可能会产生针对莱姆病螺旋体病以及其他体液免疫起保护作用的人类或兽类疾病的新型候选疫苗。
