Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, 110122, Liaoning, China.
Department of Laboratory Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
Parasit Vectors. 2021 May 7;14(1):241. doi: 10.1186/s13071-021-04743-0.
Transmission-blocking vaccine (TBV) is a promising strategy for malaria elimination. It is hypothesized that mixing or fusing two antigens targeting different stages of sexual development may provide higher transmission-blocking activity than these antigens used individually.
A chimeric protein composed of fragments of Pbg37 and PSOP25 was designed and expressed the recombinant protein in Escherichia coli Rosetta-gami B (DE3). After immunizing mice with individual recombinant proteins Pbg37 and PSOP25, mixed proteins (Pbg37+PSOP25), or the fusion protein (Pbg37-PSOP25), the antibody titers of individual sera were analyzed by ELISA. IFA and Western blot were performed to test the reactivity of the antisera with the native proteins in the parasite. The transmission-blocking activity of the different immunization schemes was assessed using in vitro and in vivo assays.
When Pbg37 and PSOP25 were co-administered in a mixture or as a fusion protein, they elicited similar antibody responses in mice as single antigens without causing immunological interference with each other. Antibodies against the mixed or fused antigens recognized the target proteins in the gametocyte, gamete, zygote, and ookinete stages. The mixed proteins or the fusion protein induced antibodies with significantly stronger transmission-reducing activities in vitro and in vivo than individual antigens.
There was no immunological interference between Pbg37 and PSOP25. The bivalent vaccines, which expand the portion of the sexual development during which the transmission-blocking antibodies act, produced significantly stronger transmission-reducing activities than single antigens. Altogether, these data provide the theoretical basis for the development of combination TBVs targeting different sexual stages.
阻断传播疫苗（TBV）是消除疟疾的一种很有前景的策略。人们假设，混合或融合针对不同性发育阶段的两种抗原可能比单独使用这些抗原提供更高的传播阻断活性。
设计了一种由 Pbg37 和 PSOP25 的片段组成的嵌合蛋白，并在大肠杆菌 Rosetta-gami B（DE3）中表达重组蛋白。用单个重组蛋白 Pbg37 和 PSOP25、混合蛋白（Pbg37+PSOP25）或融合蛋白（Pbg37-PSOP25）对小鼠进行免疫后，通过 ELISA 分析个体血清的抗体滴度。IFA 和 Western blot 用于检测抗血清与寄生虫中原位蛋白的反应性。通过体外和体内试验评估不同免疫方案的传播阻断活性。
当 Pbg37 和 PSOP25 以混合物或融合蛋白形式共同给药时，它们在小鼠中引起的抗体反应与单个抗原相似，而不会相互产生免疫干扰。针对混合或融合抗原的抗体识别配子体、配子、合子和动合子阶段的靶蛋白。混合蛋白或融合蛋白诱导的抗体在体外和体内的传播减少活性明显强于单个抗原。
Pbg37 和 PSOP25 之间没有免疫干扰。二价疫苗扩大了传播阻断抗体作用的性发育部分，产生的传播减少活性明显强于单个抗原。总的来说，这些数据为针对不同性发育阶段的组合 TBV 的开发提供了理论依据。
