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首页> 外文期刊>Vaccine >Immunogenicity of a recombinant envelope domain III protein of dengue virus type-4 with various adjuvants in mice.
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Immunogenicity of a recombinant envelope domain III protein of dengue virus type-4 with various adjuvants in mice.

机译：登革病毒4型重组包膜结构域III蛋白在小鼠中与各种佐剂的免疫原性。

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摘要

Dengue fever, a mosquito borne viral disease, has become a major public health problem with dramatic expansion in recent decades. Several dengue vaccines are at developing stage, none are yet available for humans. There is no vaccine or antiviral therapy available for dengue fever till date. Domain III of envelope protein is involved in binding to host receptors and it contains type and subtype-specific epitopes that elicit virus neutralizing antibodies. Hence domain III is an attractive vaccine candidate. In the present study we report the immunomodulatory potential of refolded D4EIII protein in combination with various adjuvants (Freunds Complete adjuvant, Montanide ISA720, Alum). Mice were tested for humoral immune responses by ELISA, immunofluorescence assay and plaque reduction neutralization test. Cell mediated immune response was tested by lymphocyte proliferation assay and cytokine profiling. All the formulations resulted in high antibody titers that neutralized the virus entry in vitro. D4EIII in combination with montanide ISA720 and Feuds complete adjuvant gave highest antibody endpoint titers followed by alum. The level of antigen-stimulated splenocyte proliferation and cytokine production was comparable to that obtained from Con A stimulation and cytokine profiling of stimulated splenocyte culture supernatants indicated that all the adjuvant formulations have induced cell mediated immune response as well. These findings suggest that D4EIII in combination with compatible adjuvants is highly immunogenic and can elicit high titer neutralizing antibodies and cell mediated immune response which plays an important role in intracellular infections, which proves that refolded D4EIII can be a potential vaccine candidate.
机译：登革热是一种由蚊子传播的病毒性疾病，在最近的几十年中，它已成为一个主要的公共卫生问题，而且急剧增加。几种登革热疫苗正处于开发阶段，尚无人类可用。迄今为止，尚无针对登革热的疫苗或抗病毒疗法。包膜蛋白的结构域III参与与宿主受体的结合，并且包含引发病毒中和抗体的类型和亚型特异性表位。因此，域III是有吸引力的疫苗候选者。在本研究中，我们报告了与多种佐剂（Freunds Complete佐剂，Montanide ISA720，Alum）结合使用的D4EIII蛋白折叠蛋白的免疫调节潜力。通过ELISA，免疫荧光测定法和噬斑减少中和试验测试小鼠的体液免疫应答。细胞介导的免疫反应通过淋巴细胞增殖测定和细胞因子谱进行测试。所有制剂均产生高抗体滴度，可中和病毒进入体外。 D4EIII与褐煤ISA720和Feuds完全佐剂联合使用时，抗体终点滴度最高，其次是明矾。抗原刺激的脾细胞增殖和细胞因子产生的水平与从Con A刺激和刺激的脾细胞培养上清液的细胞因子谱分析获得的水平相当，表明所有佐剂制剂也诱导了细胞介导的免疫应答。这些发现表明，D4EIII与相容性佐剂的结合具有很高的免疫原性，并且可以引起高滴度的中和抗体和细胞介导的免疫反应，这在细胞内感染中起着重要作用，这证明重新折叠的D4EIII可以成为潜在的疫苗候选物。

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