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Immunization with Brugia malayi Calreticulin Protein Generates Robust Antiparasitic Immunity and Offers Protection during Experimental Lymphatic Filariasis
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2021-03-05 , DOI: 10.1021/acsinfecdis.0c00565 Sunita Yadav , Pankaj Sharma , Aditi Sharma 1 , Laxmi Ganga , Jitendra Kumar Saxena 1 , Mrigank Srivastava 1
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2021-03-05 , DOI: 10.1021/acsinfecdis.0c00565 Sunita Yadav , Pankaj Sharma , Aditi Sharma 1 , Laxmi Ganga , Jitendra Kumar Saxena 1 , Mrigank Srivastava 1
Affiliation
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Lymphatic filariasis causes permanent and long-term disability worldwide. Lack of potent adulticidal drugs, the emergence of drug resistance, and the nonavailability of effective vaccines are the major drawbacks toward LF elimination. However, immunomodulatory proteins present in the parasite secretome are capable of providing good protection against LF and thus offer hope in designing new vaccines against LF. Here, we evaluated the immunogenicity and protective efficacy of B. malayi calreticulin protein (BmCRT) using in vitro and in vivo approaches. Stimulation with recombinant BmCRT (rBmCRT) significantly upregulated Th1 cytokine production in mouse splenocytes, mesenteric lymph nodes (mLNs), and splenic and peritoneal macrophages (PMΦs). Heightened NO release, ROS generation, increased lymphocyte proliferation, and increased antigen uptake were also observed after rBmCRT exposure. Mice immunized with rBmCRT responded with increased Th1 and Th2 cytokine secretion and exhibited highly elevated titers of anti-BmCRT specific IgG at day 14 and day 28 postimmunization while splenocytes and mLNs from immunized mice showed a robust recall response on restimulation with rBmCRT. Infective larvae (L3) challenge and protection studies undertaken in Mastomys coucha, a permissive model for LF, showed that rBmCRT-immunized animals mounted a robust humoral immune response as evident by elevated levels of total IgG, IgG1, IgG2a, IgG2b, and IgG3 in their serum even 150 days after L3 challenge, which led to significantly reduced microfilariae and worm burden in infected animals. BmCRT is highly immunogenic and generates robust antiparasitic immunity in immunized animals and should therefore be explored further as a putative vaccine candidate against LF.
中文翻译：
免疫与马来丝虫钙网蛋白实验淋巴丝虫病过程中会产生强大的抗寄生虫免疫和提供保护，
淋巴丝虫病在世界范围内造成永久和长期的残疾。缺乏有效的杀伤性药物，耐药性的出现以及有效疫苗的缺乏是消除LF的主要缺点。然而，存在于寄生虫分泌组中的免疫调节蛋白能够对LF提供良好的保护，因此为设计针对LF的新疫苗提供了希望。在这里，我们评估了使用体外和体内的马来芽孢杆菌钙网蛋白蛋白（BmCRT）的免疫原性和保护功效。方法。重组BmCRT（rBmCRT）刺激显着上调了小鼠脾细胞，肠系膜淋巴结（mLNs）以及脾和腹膜巨噬细胞（PMΦs）中Th1细胞因子的产生。rBmCRT暴露后还观察到NO释放增加，ROS生成，淋巴细胞增殖增加和抗原摄取增加。用rBmCRT免疫的小鼠在免疫后第14天和第28天响应增加的Th1和Th2细胞因子分泌，并显示出高度升高的抗BmCRT特异性IgG滴度，而免疫小鼠的脾细胞和mLNs在用rBmCRT再次刺激时显示出强大的召回反应。在Mastomys bencha中进行的感染性幼虫（L3）攻击和保护研究，一种允许的LF模型，rBmCRT免疫的动物表现出强大的体液免疫反应，这甚至在L3攻击后150天时血清中总IgG，IgG1，IgG2a，IgG2b和IgG3的水平升高也很明显。减少了感染动物的微丝虫病和蠕虫负担。BmCRT具有高度的免疫原性，可在免疫动物中产生强大的抗寄生虫免疫力，因此应作为可能的抗LF疫苗候选者进行进一步的研究。
更新日期：2021-04-09
中文翻译：
免疫与马来丝虫钙网蛋白实验淋巴丝虫病过程中会产生强大的抗寄生虫免疫和提供保护，
淋巴丝虫病在世界范围内造成永久和长期的残疾。缺乏有效的杀伤性药物，耐药性的出现以及有效疫苗的缺乏是消除LF的主要缺点。然而，存在于寄生虫分泌组中的免疫调节蛋白能够对LF提供良好的保护，因此为设计针对LF的新疫苗提供了希望。在这里，我们评估了使用体外和体内的马来芽孢杆菌钙网蛋白蛋白（BmCRT）的免疫原性和保护功效。方法。重组BmCRT（rBmCRT）刺激显着上调了小鼠脾细胞，肠系膜淋巴结（mLNs）以及脾和腹膜巨噬细胞（PMΦs）中Th1细胞因子的产生。rBmCRT暴露后还观察到NO释放增加，ROS生成，淋巴细胞增殖增加和抗原摄取增加。用rBmCRT免疫的小鼠在免疫后第14天和第28天响应增加的Th1和Th2细胞因子分泌，并显示出高度升高的抗BmCRT特异性IgG滴度，而免疫小鼠的脾细胞和mLNs在用rBmCRT再次刺激时显示出强大的召回反应。在Mastomys bencha中进行的感染性幼虫（L3）攻击和保护研究，一种允许的LF模型，rBmCRT免疫的动物表现出强大的体液免疫反应，这甚至在L3攻击后150天时血清中总IgG，IgG1，IgG2a，IgG2b和IgG3的水平升高也很明显。减少了感染动物的微丝虫病和蠕虫负担。BmCRT具有高度的免疫原性，可在免疫动物中产生强大的抗寄生虫免疫力，因此应作为可能的抗LF疫苗候选者进行进一步的研究。
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