Evaluation of two sexual-stage antigens as bivalent transmission-blocking vaccines in rodent malaria.
Evaluation of two sexual-stage antigens as bivalent transmission-blocking vaccines in rodent malaria.
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两种性阶段抗原作为啮齿动物疟疾二价传播阻断疫苗的评估
DOI：
10.1186/s13071-021-04743-0
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发表时间：
2021-05-07
影响因子：
3.2
通讯作者：
Cao Y
中科院分区：
文献类型：
--
作者：
Yang F;Liu F;Yu X;Zheng W;Wu Y;Qiu Y;Jin Y;Cui L;Cao Y
研究背景传播阻断疫苗（transmission-blocking vaccine，TBV）是消灭疟疾的一种有效策略。据推测，混合或融合两种针对性发育不同阶段的抗原可能会提供更高的传输阻断活性比这些抗原单独使用individuals.MethodsA嵌合蛋白组成的片段Pbg 37和PSOP 25的设计和表达重组蛋白在大肠杆菌Rosetta-gami B（DE 3）。在用单个重组蛋白Pbg 37和PSOP 25、混合蛋白（Pbg 37 + PSOP 25）或融合蛋白（Pbg 37-PSOP 25）免疫小鼠后，通过ELISA分析单个血清的抗体滴度。用免疫荧光法（IFA）和免疫印迹法（Westernblot）检测抗血清与疟原虫天然蛋白的反应性。使用在体外和体内assays.ResultsWhen Pbg 37和PSOP 25共同管理的混合物或作为融合蛋白的不同的免疫方案的传输阻断活性进行了评估，它们引起了类似的抗体反应，在小鼠中作为单一抗原，而不会引起相互免疫干扰。针对混合或融合抗原的抗体在配子母细胞、配子、合子和动合子阶段识别靶蛋白。混合蛋白或融合蛋白诱导的抗体在体外和体内具有显着更强的传输减少活动比单独的antigens.ConclusionsThere之间没有免疫干扰Pbg 37和PSOP 25。二价疫苗扩大了传播阻断抗体作用的性发育部分，比单一抗原产生了更强的减少传播的活性。总之，这些数据为开发针对不同性阶段的TBV组合提供了理论基础。
BackgroundTransmission-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.MethodsA chimeric protein composed of fragments of Pbg37 and PSOP25 was designed and expressed the recombinant protein inEscherichia coliRosetta-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.ResultsWhen 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.ConclusionsThere 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.Graphical Abstract
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影响因子：
16.1
作者：
Chen, Xiaoying;Zaro, Jennica L.;Shen, Wei-Chiang
通讯作者：
Shen, Wei-Chiang
影响因子：
5.5
作者：
Miura K;Swihart BJ;Deng B;Zhou L;Pham TP;Diouf A;Burton T;Fay MP;Long CA
通讯作者：
Long CA
影响因子：
4.5
作者：
Lima, Luciana C.;Marques, Rodolfo F.;Soares, Irene S.
通讯作者：
Soares, Irene S.
影响因子：
8.8
作者：
Angrisano F;Sala KA;Da DF;Liu Y;Pei J;Grishin NV;Snell WJ;Blagborough AM
通讯作者：
Blagborough AM
影响因子：
3.1
作者：
Duffy, PE;Kaslow, DC
通讯作者：
Kaslow, DC