Prime-boost with Chikungunya virus E2 envelope protein combined with Poly (I:C) induces specific humoral and cellular immune responses

Q4 Immunology and Microbiology Current research in immunology Pub Date : 2021-01-01 DOI:10.1016/j.crimmu.2021.03.001
Marcelo Pires Amaral , Fernanda Caroline Coirada , Juliana de Souza Apostolico , Nádia Tomita , Edgar Ruz Fernandes , Higo Fernando Santos Souza , Rosa Maria Chura-Chambi , Ligia Morganti , Silvia Beatriz Boscardin , Daniela Santoro Rosa
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引用次数: 5

Abstract

Chikungunya virus (CHIKV) is an arbovirus transmitted to humans mainly by the bite of infected Aedes aegypti and Aedes albopictus mosquitoes. CHIKV illness is characterized by fever and long-lasting arthritic symptoms, and in some cases it is a deadly disease. The CHIKV envelope E2 (E2CHIKV) glycoprotein is crucial for virus attachment to the cell. Furthermore, E2CHIKV is the immunodominant protein and the main target of neutralizing antibodies. To date, there is no available prophylactic vaccine or specific treatment against CHIKV infection. Here, we designed and produced a DNA vaccine and a recombinant protein containing a consensus sequence of E2CHIKV. C57BL/6 mice immunized twice with the E2CHIKV recombinant protein in the presence of the adjuvant Poly (I:C) induced the highest E2CHIKV-specific humoral and cellular immune responses, while the immunization with the homologous DNA vaccine pVAX-E2CHIKV was able to induce specific IFN-γ producing cells. The heterologous prime-boost strategy was also able to induce specific cellular and humoral immune responses that were, in general, lower than the responses induced by the homologous E2CHIKV recombinant protein immunization. Furthermore, recombinant E2CHIKV induced the highest titers of neutralizing antibodies. Collectively, we believe this is the first report to analyze E2CHIKV-specific humoral and cellular immune responses after immunization with E2CHIKV recombinant protein and DNA pVAX-E2CHIKV vaccine platforms.

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基孔肯雅病毒E2包膜蛋白与Poly (I:C)联合的Prime-boost可诱导特异性的体液和细胞免疫反应
基孔肯雅病毒(CHIKV)是一种主要通过受感染的埃及伊蚊和白纹伊蚊叮咬传播给人类的虫媒病毒。CHIKV疾病的特点是发烧和长期关节炎症状,在某些情况下是一种致命的疾病。CHIKV包膜E2 (E2CHIKV)糖蛋白对于病毒附着于细胞至关重要。此外,E2CHIKV是免疫优势蛋白,是中和抗体的主要靶点。迄今为止,还没有针对CHIKV感染的预防性疫苗或特异性治疗方法。在这里,我们设计并生产了含有E2CHIKV一致序列的DNA疫苗和重组蛋白。在佐剂Poly (I:C)存在的情况下,用E2CHIKV重组蛋白免疫C57BL/6小鼠可诱导最高的E2CHIKV特异性体液和细胞免疫应答,而用同源DNA疫苗pVAX-E2CHIKV免疫可诱导特异性IFN-γ产生细胞。异种启动-增强策略也能够诱导特异性细胞和体液免疫应答,总体上低于同源E2CHIKV重组蛋白免疫诱导的应答。此外,重组E2CHIKV诱导了最高滴度的中和抗体。总的来说,我们认为这是第一份分析E2CHIKV重组蛋白和DNA pVAX-E2CHIKV疫苗平台免疫后E2CHIKV特异性体液和细胞免疫反应的报告。
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