Blander S J, Horwitz M A
Department of Medicine, UCLA School of Medicine 90024.
J Immunol. 1991 Jul 1;147(1):285-91.
In a previous study, we demonstrated that immunization of guinea pigs with the major secretory protein (MSP) of Legionella pneumophila, serogroup 1 induced humoral and cell-mediated immune responses to MSP and protective immunity against lethal aerosol challenge with this serogroup of L. pneumophila. Although serogroup 1 L. pneumophila cause most cases of Legionnaires' disease, other serogroups of L. pneumophila and species of Legionella cause many cases. In this study, we have examined if immunization with MSP induces humoral and cell-mediated immune responses and protective immunity across different serogroups of L. pneumophila and species of Legionella. By immunoblot analysis, MSP from L. pneumophila serogroup 1 (Lp1 MSP), L. pneumophila serogroup 6 (Lp6 MSP), and Legionella bozemanii (Lb MSP) shared common epitopes recognized by guinea pig anti-Lp1 MSP antiserum. These MSP molecules, however, were not identical as they had different apparent m.w. Immunization of guinea pigs with MSP induced strong cell-mediated immune responses across the different serogroups and species, as indicated by splenic lymphocyte proliferation and cutaneous delayed-type hypersensitivity in response to both homologous and heterologous MSP. Immunization with MSP induced strong protective immunity across two serogroups of L. pneumophila; overall, 9 survived aerosol challenge with L. pneumophila serogroup 1 compared to 0 of 12 (0%) sham-immunized control animals (p = 3 x 10(-4), Cochran-Mantel-Haenzel chi 2 statistic for pooled data). Immunization with MSP also induced protective immunity across species of Legionella but protection was species-specific. Whereas immunization with Lb MSP induced protective immunity against L. pneumophila, neither immunization with Lp1 MSP nor immunization with Lb MSP induced protective immunity against L. bozemanii, which produces MSP. Not surprisingly, immunization with MSP did not induce protective immunity against MSP-negative Legionella micdadei. In the case of both L. bozemanii and L. micdadei, immunization with a sublethal dose did confer protective immunity to aerosol challenge indicating that these species do contain immunoprotective components. This study demonstrates that immunization with MSP induces humoral and cell-mediated immune responses across different serogroups of L. pneumophila and species of Legionella, but that the capacity of MSP immunization to induce protective immunity is species-specific. Nevertheless, an MSP vaccine has the potential to induce protective immunity against the great majority of cases of Legionnaires' disease.
在先前的一项研究中，我们证明用嗜肺军团菌血清1型的主要分泌蛋白（MSP）免疫豚鼠可诱导针对MSP的体液免疫和细胞介导的免疫反应，以及针对该血清型嗜肺军团菌致死性气溶胶攻击的保护性免疫。虽然嗜肺军团菌血清1型导致了大多数军团病病例，但其他血清型的嗜肺军团菌和军团菌属的其他菌种也导致了许多病例。在本研究中，我们检验了用MSP免疫是否能诱导针对不同血清型嗜肺军团菌和军团菌属其他菌种的体液免疫和细胞介导的免疫反应以及保护性免疫。通过免疫印迹分析，嗜肺军团菌血清1型（Lp1 MSP）、嗜肺军团菌血清6型（Lp6 MSP）和博兹曼军团菌（Lb MSP）的MSP具有豚鼠抗Lp1 MSP抗血清识别的共同表位。然而，这些MSP分子并不相同，因为它们具有不同的表观分子量。用MSP免疫豚鼠可诱导针对不同血清型和菌种的强烈细胞介导的免疫反应，脾淋巴细胞增殖以及对同源和异源MSP的皮肤迟发型超敏反应表明了这一点。用MSP免疫可诱导针对两种血清型嗜肺军团菌的强烈保护性免疫；总体而言，9只经嗜肺军团菌血清1型气溶胶攻击后存活，而12只假免疫对照动物中无一存活（0%）（p = 3×10⁻⁴，合并数据的 Cochr an - Mantel - Haenzel卡方统计量）。用MSP免疫还可诱导针对军团菌属其他菌种的保护性免疫，但保护是种属特异性的。虽然用Lb MSP免疫可诱导针对嗜肺军团菌的保护性免疫，但用Lp1 MSP免疫或用Lb MSP免疫均不能诱导针对产生MSP的博兹曼军团菌的保护性免疫。不出所料，用MSP免疫不能诱导针对无MSP的米克戴德军团菌的保护性免疫。就博兹曼军团菌和米克戴德军团菌而言，用亚致死剂量免疫确实能赋予针对气溶胶攻击的保护性免疫，这表明这些菌种确实含有免疫保护成分。本研究表明，用MSP免疫可诱导针对不同血清型嗜肺军团菌和军团菌属其他菌种的体液免疫和细胞介导的免疫反应，但MSP免疫诱导保护性免疫的能力是种属特异性的。尽管如此，一种MSP疫苗有可能诱导针对绝大多数军团病病例的保护性免疫。
