Wedlock D N, Skinner M A, de Lisle G W, Vordermeier H M, Hewinson R G, Hecker R, van Drunen Littel-van den Hurk S, Babiuk L A, Buddle B M
AgResearch, Wallaceville Animal Research Centre, P.O. Box 40063, Upper Hutt, New Zealand.
Vet Immunol Immunopathol. 2005 Jun 15;106(1-2):53-63. doi: 10.1016/j.vetimm.2005.01.002.
Culture filtrate protein (CFP) vaccines have been shown to be effective in small animal models for protecting against tuberculosis while immunisation with these types of vaccines in cattle has been less successful. A study was conducted in cattle to evaluate the ability of selected adjuvants and immunomodulators to stimulate protective immune responses to tuberculosis in animals vaccinated with Mycobacterium bovis CFP. Seven groups of cattle (n=5) were vaccinated with M. bovis CFP formulated with either Emulsigen or Polygen adjuvant alone or in combination with a specific oligodeoxynucleotides (ODN), polyinosinic acid: polycytidylic acid (poly I:C) or poly I:C and recombinant granulocyte-macrophage colony stimulating factor. Two additional groups were vaccinated subcutaneously with BCG or non-vaccinated. In contrast to the strong interferon-gamma (IFN-gamma) responses induced by BCG, the CFP vaccines induced strong antibody responses but weak IFN-gamma responses. The addition of CpG ODN to CFP significantly enhanced cell-mediated responses and elevated antibody responses to mycobacterial antigens. Of the CFP vaccinated groups, the strongest IFN-gamma responses to CFP vaccines were measured in animals vaccinated with CFP/Emulsigen+CpG or CFP/Polygen+CpG. The animals in these two groups, together with those in the BCG and non-vaccinated groups were challenged intratracheally with virulent M. bovis at 13 weeks after the first vaccination and protection was assessed, by examination for presence of tuberculous lesions in the lungs and lymph nodes, 13 weeks later at postmortem. While BCG gave the best overall protection against tuberculosis, significant protection was also seen in animals vaccinated with CFP/Emulsigen+CpG. These results establish an important role for CpG ODN in stimulating protective Th1 responses to tuberculosis in cattle and indicate that a sub-unit protein vaccine can protect these animals against tuberculosis.
已证明培养滤液蛋白（CFP）疫苗在小型动物模型中对预防结核病有效，而在牛中使用这类疫苗进行免疫接种的效果则不太理想。开展了一项针对牛的研究，以评估所选佐剂和免疫调节剂刺激接种牛分枝杆菌CFP的动物产生针对结核病的保护性免疫反应的能力。将七组牛（每组n = 5）接种单独使用乳化剂或聚佐剂配制的牛分枝杆菌CFP，或与特定的寡脱氧核苷酸（ODN）、聚肌苷酸：聚胞苷酸（聚I:C）或聚I:C与重组粒细胞-巨噬细胞集落刺激因子联合使用。另外两组分别皮下接种卡介苗或不接种疫苗。与卡介苗诱导的强烈γ干扰素（IFN-γ）反应形成对比的是，CFP疫苗诱导了强烈的抗体反应，但IFN-γ反应较弱。向CFP中添加CpG ODN可显著增强细胞介导的反应，并提高对分枝杆菌抗原的抗体反应。在接种CFP的组中，接种CFP/乳化剂+CpG或CFP/聚佐剂+CpG的动物对CFP疫苗的IFN-γ反应最强。在首次接种后13周，对这两组动物以及卡介苗接种组和未接种组的动物经气管内接种强毒力牛分枝杆菌进行攻毒，并在13周后的尸检时通过检查肺部和淋巴结中结核病变的存在情况来评估保护效果。虽然卡介苗对结核病提供了最佳的总体保护，但在接种CFP/乳化剂+CpG的动物中也观察到了显著的保护作用。这些结果证实了CpG ODN在刺激牛对结核病产生保护性Th1反应中的重要作用，并表明亚单位蛋白疫苗可以保护这些动物免受结核病侵害。
