Amaral Marcelo Pires, Coirada Fernanda Caroline, de Souza Apostolico Juliana, Tomita Nádia, Fernandes Edgar Ruz, Santos Souza Higo Fernando, Chura-Chambi Rosa Maria, Morganti Ligia, Boscardin Silvia Beatriz, Rosa Daniela Santoro
Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil.
Institute for Investigation in Immunology (iii), INCT, São Paulo, Brazil.
Curr Res Immunol. 2021 Mar 17;2:23-31. doi: 10.1016/j.crimmu.2021.03.001. eCollection 2021.
Chikungunya virus (CHIKV) is an arbovirus transmitted to humans mainly by the bite of infected and 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 (E2) glycoprotein is crucial for virus attachment to the cell. Furthermore, E2 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 E2. C57BL/6 mice immunized twice with the E2 recombinant protein in the presence of the adjuvant Poly (I:C) induced the highest E2-specific humoral and cellular immune responses, while the immunization with the homologous DNA vaccine pVAX-E2 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 E2 recombinant protein immunization. Furthermore, recombinant E2 induced the highest titers of neutralizing antibodies. Collectively, we believe this is the first report to analyze E2-specific humoral and cellular immune responses after immunization with E2 recombinant protein and DNA pVAX-E2 vaccine platforms.
基孔肯雅病毒(CHIKV)是一种虫媒病毒,主要通过受感染蚊子的叮咬传播给人类。基孔肯雅病毒病的特征是发热和持久的关节炎症状,在某些情况下,它是一种致命疾病。基孔肯雅病毒包膜E2(E2)糖蛋白对于病毒附着于细胞至关重要。此外,E2是免疫显性蛋白,也是中和抗体的主要靶点。迄今为止,尚无针对基孔肯雅病毒感染的预防性疫苗或特异性治疗方法。在此,我们设计并制备了一种DNA疫苗和一种包含E2共有序列的重组蛋白。在佐剂聚肌胞苷酸(Poly (I:C))存在下,用E2重组蛋白对C57BL/6小鼠进行两次免疫,诱导出最高的E2特异性体液免疫和细胞免疫反应,而用同源DNA疫苗pVAX-E2免疫能够诱导产生特异性干扰素-γ的细胞。异源初免-加强策略也能够诱导特异性细胞免疫和体液免疫反应,总体上低于同源E2重组蛋白免疫诱导的反应。此外,重组E2诱导出最高滴度的中和抗体。总体而言,我们认为这是第一份分析用E2重组蛋白和DNA pVAX-E2疫苗平台免疫后E2特异性体液免疫和细胞免疫反应的报告。