Department of Microbiology and Immunology, Biosciences Institute, São Paulo State University, Botucatu, Brazil.
Neuroimmunomodulation. 2010;17(5):287-97. doi: 10.1159/000292018. Epub 2010 Apr 17.
A DNA vaccine (pVAXhsp65) containing the gene of a heat-shock protein (hsp65) from Mycobacterium leprae showed high immunogenicity and protective efficacy against tuberculosis in BALB/c mice. A possible deleterious effect related to autoimmunity needed to be tested because hsp65 is highly homologous to the correspondent mammalian protein. In this investigation we tested the effect of a previous immunization with DNAhsp65 in the development of experimental autoimmune encephalomyelitis (EAE), a rat model of multiple sclerosis.
Female Lewis rats were immunized with 3 pVAXhsp65 doses by intramuscular route. Fifteen days after the last DNA dose the animals were evaluated for specific immunity or submitted to induction of EAE. Animals were evaluated daily for weight loss and clinical score, and euthanized during the recovery phase to assess the immune response and inflammatory infiltration at the central nervous system.
Immunization with pVAXhsp65 induced a specific immune response characterized by production of IgG(2b) anti-hsp65 antibodies and IFN-gamma secretion. Previous immunization with pVAXhsp65 did not change EAE clinical manifestations (weight and clinical score). However, the vaccine clearly decreased brain and lumbar spinal cord inflammation. In addition, it downmodulated IFN-gamma and IL-10 production by peripheral lymphoid organs.
Our data demonstrated that this vaccine does not trigger a deleterious effect on EAE development and also points to a potential protective effect.
一种含有麻风分枝杆菌热休克蛋白（hsp65）基因的 DNA 疫苗（pVAXhsp65）在 BALB/c 小鼠中显示出了高度的免疫原性和对结核病的保护效力。由于 hsp65 与相应的哺乳动物蛋白高度同源，因此需要测试与自身免疫相关的可能有害影响。在这项研究中，我们测试了先前用 DNAhsp65 免疫对实验性自身免疫性脑脊髓炎（EAE）的影响，EAE 是多发性硬化症的大鼠模型。
雌性 Lewis 大鼠通过肌肉内途径用 3 个 pVAXhsp65 剂量进行免疫。在最后一次 DNA 剂量后 15 天，对动物进行特异性免疫评估或进行 EAE 诱导。每天评估动物的体重减轻和临床评分，并在恢复期处死动物，以评估中枢神经系统的免疫反应和炎症浸润。
pVAXhsp65 免疫诱导了特异性免疫反应，其特征为产生 IgG(2b)抗 hsp65 抗体和 IFN-γ分泌。先前用 pVAXhsp65 免疫并未改变 EAE 的临床表现（体重和临床评分）。然而，该疫苗明显减轻了脑和腰椎脊髓的炎症。此外，它还下调了外周淋巴器官中 IFN-γ和 IL-10 的产生。
我们的数据表明，该疫苗不会对 EAE 的发展产生有害影响，并且还具有潜在的保护作用。
