Blander S J, Horwitz M A
Department of Medicine, UCLA School of Medicine 90024.
J Clin Invest. 1991 Mar;87(3):1054-9. doi: 10.1172/JCI115065.
We have examined the capacity of Legionella pneumophila membranes to induce cell-mediated immune responses and protective immunity in a guinea pig model of Legionnaires' disease. Guinea pigs immunized by aerosol with L. pneumophila membranes developed strong cell-mediated immune responses to L. pneumophila membranes as demonstrated by cutaneous delayed-type hypersensitivity and in vitro splenic lymphocyte proliferation. Guinea pigs immunized by aerosol or by subcutaneous inoculation with L. pneumophila membranes developed strong protective immunity against lethal aerosol challenge with L. pneumophila. Overall, in six independent experiments, 39 of 49 (80%) guinea pigs immunized with L. pneumophila membranes survived challenge compared with 2 of 40 (5%) sham-immunized controls (P = 2 x 10(-13). In contrast, guinea pigs immunized by aerosol with formalin-killed L. pneumophila did not develop either a strong cell-mediated immune response to L. pneumophila antigens or protective immunity to lethal aerosol challenge. The capacity of L. pneumophila membranes to induce protective immunity was independent of the major secretory protein of L. pneumophila, which we previously demonstrated is an immunoprotective molecule. Purified L. pneumophila membranes did not contain detectable major secretory protein (MSP) on immunoblots; immunization of guinea pigs with L. pneumophila membranes did not induce anti-MSP antibody; and guinea pigs developed comparable protective immunity after immunization with membranes from either an L. pneumophila strain that secretes the major secretory protein or an isogenic mutant that does not. This study demonstrates that (a) immunization with L. pneumophila membranes but not formalin-killed L. pneumophila induces strong cell-mediated immune responses and protective immunity, (b) L. pneumophila membranes contain immunoprotective molecules distinct from the major secretory protein of L. pneumophila, and (c) L. pneumophila membranes have potential as a vaccine against Legionnaires' disease.
我们在豚鼠军团病模型中研究了嗜肺军团菌膜诱导细胞介导免疫反应和保护性免疫的能力。通过气溶胶用嗜肺军团菌膜免疫的豚鼠对嗜肺军团菌膜产生了强烈的细胞介导免疫反应，这通过皮肤迟发型超敏反应和体外脾淋巴细胞增殖得以证明。通过气溶胶或皮下接种用嗜肺军团菌膜免疫的豚鼠对嗜肺军团菌致死性气溶胶攻击产生了强大的保护性免疫。总体而言，在六个独立实验中，49只经嗜肺军团菌膜免疫的豚鼠中有39只（80%）在攻击后存活，而40只假免疫对照豚鼠中只有2只（5%）存活（P = 2×10⁻¹³）。相比之下，通过气溶胶用福尔马林灭活的嗜肺军团菌免疫的豚鼠既未对嗜肺军团菌抗原产生强烈的细胞介导免疫反应，也未对致死性气溶胶攻击产生保护性免疫。嗜肺军团菌膜诱导保护性免疫的能力与嗜肺军团菌的主要分泌蛋白无关，我们之前证明该蛋白是一种免疫保护分子。纯化的嗜肺军团菌膜在免疫印迹上未检测到可检测的主要分泌蛋白（MSP）；用嗜肺军团菌膜免疫豚鼠未诱导产生抗MSP抗体；并且用分泌主要分泌蛋白的嗜肺军团菌菌株或不分泌该蛋白的同基因突变体的膜免疫后，豚鼠产生了相当的保护性免疫。这项研究表明：（a）用嗜肺军团菌膜免疫而非福尔马林灭活的嗜肺军团菌可诱导强烈的细胞介导免疫反应和保护性免疫；（b）嗜肺军团菌膜含有与嗜肺军团菌主要分泌蛋白不同的免疫保护分子；（c）嗜肺军团菌膜有作为军团病疫苗的潜力。
