Floden Angela M, Gonzalez Tammy, Gaultney Robert A, Brissette Catherine A
Department of Microbiology and Immunology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USA.
Clin Vaccine Immunol. 2013 Jun;20(6):892-9. doi: 10.1128/CVI.00758-12. Epub 2013 Apr 17.
Previous studies indicated that the Lyme disease spirochete Borrelia burgdorferi expresses the RevA outer surface protein during mammalian infection. As an adhesin that promotes bacterial interaction with fibronectin, RevA appears to be a good target for preventive therapies. RevA proteins are highly conserved across all Lyme borreliae, and antibodies against RevA protein are cross-reactive among RevA proteins from diverse strains. Mice infected with B. burgdorferi mounted a rapid IgM response to RevA, followed by a strong IgG response that generally remained elevated for more than 12 months, suggesting continued exposure of RevA protein to the immune system. RevA antibodies were bactericidal in vitro. To evaluate the RevA antigen as a potential vaccine, mice were vaccinated with recombinant RevA and challenged with B. burgdorferi by inoculation with a needle or by a tick bite. Cultured tissues from all treatment groups were positive for B. burgdorferi. Vaccinated animals also appeared to have similar levels of B. burgdorferi DNA compared to nonvaccinated controls. Despite its antigenicity, surface expression, and the production of bactericidal antibodies against it, RevA does not protect against Borrelia burgdorferi infection in a mouse model. However, passive immunization with anti-RevA antibodies did prevent infection, suggesting the possible utility of RevA-based immunotherapeutics or vaccine.
先前的研究表明,莱姆病螺旋体伯氏疏螺旋体在哺乳动物感染期间表达RevA外表面蛋白。作为一种促进细菌与纤连蛋白相互作用的黏附素,RevA似乎是预防性治疗的一个良好靶点。RevA蛋白在所有莱姆疏螺旋体中高度保守,针对RevA蛋白的抗体在来自不同菌株的RevA蛋白之间具有交叉反应性。感染伯氏疏螺旋体的小鼠对RevA产生了快速的IgM反应,随后是强烈的IgG反应,这种反应通常会持续升高超过12个月,这表明RevA蛋白持续暴露于免疫系统。RevA抗体在体外具有杀菌作用。为了评估RevA抗原作为一种潜在疫苗的效果,用重组RevA对小鼠进行免疫接种,然后通过针刺接种或蜱叮咬用伯氏疏螺旋体对其进行攻击。所有治疗组的培养组织中伯氏疏螺旋体均呈阳性。与未接种疫苗的对照组相比,接种疫苗的动物体内伯氏疏螺旋体DNA水平似乎也相似。尽管RevA具有抗原性、表面表达以及针对它产生杀菌抗体,但在小鼠模型中RevA并不能预防伯氏疏螺旋体感染。然而,用抗RevA抗体进行被动免疫确实可以预防感染,这表明基于RevA的免疫疗法或疫苗可能具有实用性。