Stäger S, Smith D F, Kaye P M
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
J Immunol. 2000 Dec 15;165(12):7064-71. doi: 10.4049/jimmunol.165.12.7064.
Vaccination against visceral leishmaniasis has received limited attention compared with cutaneous leishmaniasis, although the need for an effective vaccine against visceral leishmaniasis is pressing. In this study, we demonstrate for the first time that a recombinant stage-specific hydrophilic surface protein of Leishmania donovani, recombinant hydrophilic acylated surface protein B1 (HASPB1), is able to confer protection against experimental challenge. Protection induced by rHASPB1 does not require adjuvant and, unlike soluble Leishmania Ag + IL-12, extends to the control of parasite burden in the spleen, an organ in which parasites usually persist and are refractory to a broad range of immunological and chemotherapeutic interventions. Both immunohistochemistry (for IL-12p40) and enzyme-linked immunospot assay (for IL-12p70) indicate that immunization with rHASPB1 results in IL-12 production by dendritic cells, although an analysis of Ab isotype responses to rHASPB1 suggests that this response is not sufficient in magnitude to induce a polarized Th1 response. Although both vaccinated and control-infected mice have equivalent frequencies of rHASPB1-specific CD4(+) T cells producing IFN-gamma, vaccine-induced protection correlates with the presence of rHASPB1-specific, IFN-gamma-producing CD8(+) T cells. Thus, we have identified a novel vaccine candidate Ag for visceral leishmaniasis, which appears to operate via a mechanism similar to that previously associated with DNA vaccination.
与皮肤利什曼病相比，内脏利什曼病的疫苗接种受到的关注较少，尽管针对内脏利什曼病的有效疫苗的需求迫在眉睫。在本研究中，我们首次证明，杜氏利什曼原虫的重组阶段特异性亲水性表面蛋白，即重组亲水性酰化表面蛋白B1（HASPB1），能够提供针对实验性攻击的保护作用。rHASPB1诱导的保护作用不需要佐剂，并且与可溶性利什曼原虫抗原+IL-12不同，它还能控制脾脏中的寄生虫负荷，寄生虫通常在脾脏中持续存在，并且对广泛的免疫和化学治疗干预具有抗性。免疫组织化学（检测IL-12p40）和酶联免疫斑点分析（检测IL-12p70）均表明，用rHASPB1免疫可导致树突状细胞产生IL-12，尽管对rHASPB1的抗体亚型反应分析表明，这种反应的强度不足以诱导极化的Th1反应。尽管接种疫苗的小鼠和对照感染小鼠产生IFN-γ的rHASPB1特异性CD4(+) T细胞频率相当，但疫苗诱导的保护作用与rHASPB1特异性、产生IFN-γ的CD8(+) T细胞的存在相关。因此，我们已经确定了一种用于内脏利什曼病的新型候选疫苗抗原，其作用机制似乎与先前与DNA疫苗接种相关的机制相似。
