A Multistage Formulation Based on Full-Length CSP and AMA-1 Ectodomain ofPlasmodium vivaxInduces High Antibody Titers and T-cells and Partially Protects Mice Challenged with a TransgenicPlasmodium bergheiParasite
A Multistage Formulation Based on Full-Length CSP and AMA-1 Ectodomain ofPlasmodium vivaxInduces High Antibody Titers and T-cells and Partially Protects Mice Challenged with a TransgenicPlasmodium bergheiParasite
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DOI：
10.3390/microorganisms8060916
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发表时间：
2020-06-01
期刊：
影响因子：
4.5
通讯作者：
Soares, Irene S.
中科院分区：
文献类型：
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作者：
Lima, Luciana C.;Marques, Rodolfo F.;Soares, Irene S.
在美洲占主导地位的疟原虫感染，占疟疾病例的75％。实际上，先前被认为是良性的疟疾，这是一种高度令人衰弱且经济上重要的疾病。考虑到疟疾寄生虫生命周期的高复杂性，已经假设针对质量菌的有效疫苗制剂应包含在不同寄生虫阶段表达的多种抗原。基于此，我们分析了重组剂。 VivaxVaccine配方混合了顶端膜抗原1型域（PVAMA-1）和先前由我们组研究的全长围孢蛋白蛋白（PVCSP-ALL（FL））混合，这会引起小鼠的有效抗体反应。在poly（i：c）辅助剂，TLR3激动剂的存在下，单独或组合将遗传上不同的小鼠菌株（C57BL/6和BALB/C）与蛋白质免疫。在C57BL/6中，对PVAMA-1和三个PVCSP变体（VK210，VK247和p。vivax类）诱导了高抗体滴度。同时，将PVAMA-1与PVCSP-ALL（FL）混合对持久的总IgG抗体滴度没有影响。此外，通过免疫荧光测定法，免疫小鼠的抗体识别为VK210孢子虫和血液阶段寄生虫。但是，在BALB/C模型中，针对PVCSP-ALL（FL）的抗体反应相对较低。在C57BL/6小鼠中观察到PVAMA-1特异性CD3（+）CD4（+）和CD3（+）CD8（+）CD-Cell响应，并且PVCSP-ALL（FL）组合会损害细胞反应。更相关的是，多阶段疫苗配方为表达同源PVCSP蛋白的转晶质流质虫虫虫挑战的小鼠提供了部分保护。
Infections withPlasmodium vivaxare predominant in the Americas, representing 75% of malaria cases. Previously perceived as benign, malaria vivax is, in fact, a highly debilitating and economically important disease. Considering the high complexity of the malaria parasite life cycle, it has been hypothesized that an effective vaccine formulation againstPlasmodiumshould contain multiple antigens expressed in different parasite stages. Based on that, we analyzed a recombinantP. vivaxvaccine formulation mixing the apical membrane antigen 1 ectodomain (PvAMA-1) and a full-length circumsporozoite protein (PvCSP-All(FL)) previously studied by our group, which elicits a potent antibody response in mice. Genetically distinct strains of mice (C57BL/6 and BALB/c) were immunized with the proteins, alone or in combination, in the presence of poly(I:C) adjuvant, a TLR3 agonist. In C57BL/6, high-antibody titers were induced against PvAMA-1 and the three PvCSP variants (VK210, VK247, andP. vivax-like). Meanwhile, mixing PvAMA-1 with PvCSP-All(FL)had no impact on total IgG antibody titers, which were long-lasting. Moreover, antibodies from immunized mice recognized VK210 sporozoites and blood-stage parasites by immunofluorescence assay. However, in the BALB/c model, the antibody response against PvCSP-All(FL)was relatively low. PvAMA-1-specific CD3(+)CD4(+)and CD3(+)CD8(+)T-cell responses were observed in C57BL/6 mice, and the cellular response was impaired by PvCSP-All(FL)combination. More relevant, the multistage vaccine formulation provided partial protection in mice challenged with a transgenicPlasmodium bergheisporozoite expressing the homologous PvCSP protein.