Animal Disease Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Pullman, WA 99164-7030, USA.
Vaccine. 2010 May 7;28(21):3741-7. doi: 10.1016/j.vaccine.2010.02.067. Epub 2010 Mar 1.
Many vector-borne pathogens evade clearance via rapid variation in their immunogenic surface expressed proteins. This is exemplified by Anaplasma marginale, a tick-borne bacterial pathogen that generates major surface protein 2 (Msp2) variants to provide for immune escape and allow long-term pathogen persistence. In contrast to persistence following infection, immunization with a surface protein complex, which includes Msp2, induces a response that prevents infection upon challenge. We hypothesized that the immune response induced by immunization altered the anti-Msp2 antibody repertoire as compared to that induced during infection, shifting the immune response toward conserved and thus broadly protective epitopes. The antibody response to the conserved (CR) and hypervariable (HVR) regions encoded by the full set of msp2 variant alleles was determined for immunized animals prior to challenge and non-immunized, infected animals. While both groups of animals had a similar antibody repertoire in terms of breath and magnitude, the titers to the Msp2 CR were strongly correlated (p<0.005) with control of bacteremia only in the infected animals. Among the immunized animals, there was no correlation between the breadth or magnitude of the anti-Msp2 antibody response and either complete protection from infection or control of bacteremia. This is consistent with separate immunologic mechanisms being responsible for control of bacteremia in infected animals as compared to immunized animals and suggests that conserved outer membrane proteins other than Msp2 are responsible for the complete clearance observed following challenge of vaccinees.
许多虫媒病原体通过其免疫原性表面表达蛋白的快速变异来逃避清除。这方面的一个例子是边缘无浆体(Anaplasma marginale),一种蜱传细菌性病原体,它产生主要表面蛋白 2(Msp2)变体,以提供免疫逃逸并允许病原体长期存在。与感染后的持续存在不同,用包括 Msp2 在内的表面蛋白复合物进行免疫接种会引发一种反应,使动物在受到挑战时不会被感染。我们假设,与感染期间诱导的免疫反应相比,免疫接种诱导的抗 Msp2 抗体库发生了变化,使免疫反应转向保守且因此具有广泛保护作用的表位。在挑战之前和未免疫感染的动物中,测定了针对完整 Msp2 变体等位基因编码的保守(CR)和高变(HVR)区的抗体反应。尽管两组动物在抗体库的广度和幅度方面都相似,但 Msp2 CR 的滴度与感染动物中菌血症的控制呈强烈相关性(p<0.005)。在免疫接种的动物中,抗 Msp2 抗体反应的广度或幅度与完全免受感染或控制菌血症之间均无相关性。这与感染动物和免疫接种动物控制菌血症的免疫机制不同是一致的,并表明除了 Msp2 之外的其他保守外膜蛋白负责在疫苗接种者受到挑战后观察到的完全清除。