Center for Infectious Disease & Immunity, Department of Internal Medicine, The University of New Mexico Health Science Center, Albuquerque, New Mexico, USA.
Infect Immun. 2011 Apr;79(4):1770-8. doi: 10.1128/IAI.00605-10. Epub 2011 Jan 31.
Pneumonic tularemia is a life-threatening disease caused by inhalation of the highly infectious intracellular bacterium Francisella tularensis. The most serious form of the disease associated with the type A strains can be prevented in experimental animals through vaccination with the attenuated live vaccine strain (LVS). The protection is largely cell mediated, but the contribution of antibodies remains controversial. We addressed this issue in a series of passive immunization studies in Fischer 344 (F344) rats. Subcutaneous LVS vaccination induced a robust serum antibody response dominated by IgM, IgG2a, and IgG2b antibodies. Prophylactic administration of LVS immune serum or purified immune IgG reduced the severity and duration of disease in naïve rats challenged intratracheally with a lethal dose of the virulent type A strain SCHU S4. The level of resistance increased with the volume of immune serum given, but the maximum survivable SCHU S4 challenge dose was at least 100-fold lower than that shown for LVS-vaccinated rats. Protection correlated with reduced systemic bacterial growth, less severe histopathology in the liver and spleen during the early phase of infection, and bacterial clearance by a T cell-dependent mechanism. Our results suggest that treatment with immune serum limited the sequelae associated with infection, thereby enabling a sterilizing T cell response to develop and resolve the infection. Thus, antibodies induced by LVS vaccination may contribute to the defense of F344 rats against respiratory infection by type A strains of F. tularensis.
肺鼠疫是一种由高度传染性的细胞内细菌弗朗西斯菌引起的危及生命的疾病。通过用减毒活疫苗株（LVS）接种，可以预防与 A 型菌株相关的最严重形式的疾病。这种保护主要是细胞介导的，但抗体的贡献仍存在争议。我们在一系列 Fischer 344（F344）大鼠的被动免疫研究中解决了这个问题。皮下 LVS 疫苗接种会引起强烈的血清抗体反应，主要由 IgM、IgG2a 和 IgG2b 抗体组成。预防性给予 LVS 免疫血清或纯化的免疫 IgG 可降低未经免疫的大鼠经气管内接受致命剂量的强毒 A 型菌株 SCHU S4 攻击时的疾病严重程度和持续时间。随着免疫血清量的增加，抵抗力增加，但最大可耐受的 SCHU S4 挑战剂量至少比 LVS 疫苗接种大鼠低 100 倍。保护与全身细菌生长减少、感染早期肝和脾的组织病理学变化减轻以及依赖 T 细胞的机制清除细菌有关。我们的结果表明，用免疫血清治疗可限制感染相关的后遗症，从而使杀菌性 T 细胞反应得以发展并解决感染。因此，LVS 疫苗接种诱导的抗体可能有助于 F344 大鼠抵御 A 型弗朗西斯菌的呼吸道感染。
