Bargieri Daniel Y, Rosa Daniela S, Braga Catarina J M, Carvalho Bruna O, Costa Fabio T M, Espíndola Noeli Maria, Vaz Adelaide José, Soares Irene S, Ferreira Luis C S, Rodrigues Mauricio M
Centro Interdisciplinar de Terapia Gênica (CINTERGEN), Universidade Federal de São Paulo, Escola Paulista de Medicina, Rua Mirassol 207, São Paulo, SP, Brazil.
Vaccine. 2008 Nov 11;26(48):6132-42. doi: 10.1016/j.vaccine.2008.08.070. Epub 2008 Sep 18.
The present study evaluated the immunogenicity of new malaria vaccine formulations based on the 19kDa C-terminal fragment of Plasmodium vivax Merozoite Surface Protein-1 (MSP1(19)) and the Salmonella enterica serovar Typhimurium flagellin (FliC), a Toll-like receptor 5 (TLR5) agonist. FliC was used as an adjuvant either admixed or genetically linked to the P. vivax MSP1(19) and administered to C57BL/6 mice via parenteral (s.c.) or mucosal (i.n.) routes. The recombinant fusion protein preserved MSP1(19) epitopes recognized by sera collected from P. vivax infected humans and TLR5 agonist activity. Mice parenterally immunized with recombinant P. vivax MSP1(19) in the presence of FliC, either admixed or genetically linked, elicited strong and long-lasting MSP1(19)-specific systemic antibody responses with a prevailing IgG1 subclass response. Incorporation of another TLR agonist, CpG ODN 1826, resulted in a more balanced response, as evaluated by the IgG1/IgG2c ratio, and higher cell-mediated immune response measured by interferon-gamma secretion. Finally, we show that MSP1(19)-specific antibodies recognized the native protein expressed on the surface of P. vivax parasites harvested from infected humans. The present report proposes a new class of malaria vaccine formulation based on the use of malarial antigens and the innate immunity agonist FliC. It contains intrinsic adjuvant properties and enhanced ability to induce specific humoral and cellular immune responses when administered alone or in combination with other adjuvants.
本研究评估了基于间日疟原虫裂殖子表面蛋白-1(MSP1(19))19kDa C端片段和鼠伤寒沙门氏菌鞭毛蛋白(FliC,一种Toll样受体5(TLR5)激动剂)的新型疟疾疫苗制剂的免疫原性。FliC用作佐剂,与间日疟原虫MSP1(19)混合或基因连接,并通过非肠道(皮下)或黏膜(鼻内)途径给予C57BL/6小鼠。重组融合蛋白保留了被间日疟原虫感染人类血清识别的MSP1(19)表位以及TLR5激动剂活性。在FliC存在下,通过皮下或基因连接方式用重组间日疟原虫MSP1(19)对小鼠进行非肠道免疫,引发了强烈且持久的MSP1(19)特异性全身抗体反应,主要为IgG1亚类反应。加入另一种TLR激动剂CpG ODN 1826后,通过IgG1/IgG2c比值评估,反应更加平衡,通过干扰素-γ分泌测量的细胞介导免疫反应更高。最后,我们表明MSP1(19)特异性抗体识别从感染人类中收获的间日疟原虫寄生虫表面表达的天然蛋白。本报告提出了一类基于使用疟疾抗原和固有免疫激动剂FliC的新型疟疾疫苗制剂。它具有内在佐剂特性,单独使用或与其他佐剂联合使用时,诱导特异性体液和细胞免疫反应的能力增强。
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