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首页> 外文期刊>Infection and immunity >Resistance to Coccidioides immitis in Mice after Immunization with Recombinant Protein or a DNA Vaccine of a Proline-Rich Antigen
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Resistance to Coccidioides immitis in Mice after Immunization with Recombinant Protein or a DNA Vaccine of a Proline-Rich Antigen

机译:重组蛋白或富含脯氨酸抗原的DNA疫苗免疫后对小鼠球虫免疫的抵抗

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Two inbred strains of mice (BALB/c and C57BL/6) were vaccinated with either recombinant expression protein of a Coccidioides immitis spherule-derived proline-rich antigen (rPRA) in monophosphoryl lipid A-oil emulsion adjuvant or a DNA vaccine based on the same antigen. Four weeks after vaccination, mice were infected intraperitoneally with arthroconidia. By 2 weeks, groups of mice receiving saline or plasmids with no PRA insert exhibited significant weight loss, and quantitative CFUs in the lungs ranged from 5.9 to 6.4 log10. In contrast, groups of mice immunized with either rPRA or DNA vaccine had significantly smaller pulmonary fungal burdens, ranging from 3.0 to 4.5 log10 fewer CFUs. In vitro immunologic markers of lymphocyte proliferation and gamma interferon (IFN-γ) release after splenocytes were stimulated with rPRA correlated with protection. Also, plasma concentrations of rPRA-specific total immunoglobulin G (IgG), IgG1, and IgG2a showed increases in vaccinated mice. These studies expand earlier work by demonstrating protection in mice which differ in H-2background, by using an adjuvant that is potentially applicable to human use, and by achieving comparable protections with a DNA-based vaccine. Our in vitro results substantiate a Th1 response as evidenced by IFN-γ release and increased IgG2a. However, IgG1 was also stimulated, suggesting some Th2 response as well. PRA is a promising vaccine candidate for prevention of coccidioidomycosis and warrants further investigation.
机译:在单磷酰脂质A油乳剂佐剂中,对两种自交系小鼠(BALB / c和C57BL / 6)接种了球孢子虫免疫球蛋白-脯氨酸-富含脯氨酸的抗原(rPRA)的重组表达蛋白或基于相同抗原的DNA疫苗。疫苗接种后四周,小鼠腹膜内感染了关节炎。到2周时,接受盐水或不含PRA插入物的质粒的小鼠组显示出明显的体重减轻,并且肺中定量CFU的范围为5.9至6.4 log 10 。相比之下,用rPRA或DNA疫苗免疫的小鼠组的肺真菌负担明显减少,CFU减少了3.0至4.5 log 10 。 rPRA刺激脾细胞后,淋巴细胞增殖和γ干扰素(IFN-γ)释放的体外免疫标记与保护作用有关。同样,rPRA特异性总免疫球蛋白G(IgG),IgG1和IgG2a的血浆浓度在接种疫苗的小鼠中显示增加。这些研究通过证明对 H-2 背景不同的小鼠的保护作用,使用可能适用于人类的佐剂以及通过基于DNA的疫苗实现类似的保护作用,扩大了早期的工作。我们的体外结果证实了Th1应答,如IFN-γ释放和IgG2a升高所证明。但是,IgG1也受到刺激,也暗示了一些Th2反应。 PRA是预防球虫病的有前途的候选疫苗,值得进一步研究。

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