Significant passive protective effect against anthrax by antibody to Bacillus anthracis inactivated spores that lack two virulence plasmids
Significant passive protective effect against anthrax by antibody to Bacillus anthracis inactivated spores that lack two virulence plasmids
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DOI：
10.1099/mic.0.28788-0
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发表时间：
2006-10-01
期刊：
影响因子：
2.8
通讯作者：
Makino, Sou-ichi
中科院分区：
文献类型：
--
作者：
Enkhtuya, Jargalsaikhan;Kawamoto, Keiko;Makino, Sou-ichi
基于保护性抗原（PA）的无细胞疫苗是唯一获准用于预防人类炭疽杆菌感染的疫苗。虽然PA显示出很强的免疫原性，但荚膜或孢子相关的体细胞抗原可能是重要的额外疫苗靶点，以充分保护炭疽。在这项研究中，孢子相关抗原对B。确定炭疽感染。用福尔马林固定的非致炎性未包囊B孢子免疫家兔。对缺失两种毒力质粒pXO 1和pXO 2的炭疽菌株进行免疫，并评价免疫抗体的保护作用。免疫组化和Western blot分析表明，抗B。炭疽（抗BA）-孢子IgG特异性结合到B的孢子或内生孢子的表面。炭疽杆菌，但不对营养细胞，或密切相关的芽孢杆菌属物种，如蜡状芽孢杆菌、枯草芽孢杆菌和苏云金芽孢杆菌。被动转移的抗BA孢子IgG保护小鼠免受致死剂量的完全毒性B的腹膜内攻击。炭疽孢子，并以剂量依赖性方式增加存活率。孢子与抗体的预孵育也以剂量依赖性方式降低其感染性。细菌数量（c.f.u.）在感染小鼠的脾脏和肝脏中，抗体处理的小鼠比未处理的小鼠显著降低。用抗BA孢子IgG处理也抑制J774.1巨噬细胞中孢子的萌发，表明孢子的调理作用促进巨噬细胞的吞噬作用和随后的杀伤。这些结果表明孢子表面抗原作为疫苗靶标的有用性。与主要毒力因子如PA结合，孢子相关抗原可能为B提供更安全和更有效的多组分疫苗。炭疽感染。
The protective-antigen (PA)-based cell-free vaccine is the only vaccine licensed for use against Bacillus anthracis infection in humans. Although the PA shows strong immunogenicity, the capsule or spore-associated somatic antigens may be important as additional vaccine targets for full protection against anthrax. In this study, the protective effect of spore-associated antigens against B. anthracis infection was determined. Rabbits were immunized with formalin-fixed spores of a non-toxigenic unencapsulated B. anthracis strain that lacked the two virulence plasmids pXO1 and pXO2, and the protective effects of the immune antibody were evaluated. Immunostaining and Western blot analysis revealed that the anti-B. anthracis (anti-BA)-spore IgG specifically bound to the surface of spores or endospores of B. anthracis, but not to vegetative cells, or closely related Bacillus species, such as Bacillus cereus, Bacillus subtilis and Bacillus thuringiensis. Passively transferred anti-BA-spore IgG protected mice from intraperitoneal challenge with a lethal dose of fully virulent B. anthracis spores, and increased the survival rate in a dose-dependent manner. Pre-incubation of spores with antibody also reduced their infectivity in a dose-dependent manner. The number of bacteria (c.f.u.) in spleens and livers of infected mice was significantly lower in antibody-treated mice than in untreated mice. Treatment with anti-BA-spore IgG also inhibited the germination of spores in J774.1 macrophages, suggesting that opsonization of spores promotes phagocytosis and subsequent killing by macrophages. These results indicate the usefulness of spore surface antigens as vaccine targets. In combination with major virulence factors such as the PA, spore-associated antigens may offer a safer and more effective multicomponent vaccine for B. anthracis infection.