Characterization of PSOP26 as an ookinete surface antigen with improved transmission-blocking activity when fused with PSOP25

• Published in: Parasites & vectors Vol. 15; no. 1; p. 175
• Main Authors: Wang, Peng-peng, Jiang, Xuefeng, Bai, Jie, Yang, Fan, Yu, Xinxin, Wu, Yudi, Zheng, Wenqi, Zhang, Yongzhe, Cui, Liwang, Liu, Fei, Zhu, Xiaotong, Cao, Yaming
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 23.05.2022; BioMed Central; BMC
• Subjects: Antibodies; Antigens; Antisera; Aquatic insects; blood serum; Cellular proteins; Chimeras; Clinical trials; Cloning; E coli; ELISA; Enzyme-linked immunosorbent assay; Escherichia coli; Fertilization; fluorescent antibody technique; Fusion protein; Gamete; Gametes; Gametogenesis; Gene disruption; Gene expression; gene targeting; Genetic aspects; Health aspects; Immunization; Immunoassay; Immunoassays; Immunofluorescence; Immunogenicity; Immunology; Infections; Malaria; mosquito vectors; Mosquitoes; oocysts; Ookinete; ookinetes; Parasite antigens; Parasites; Plasmodium; Plasmodium berghei; Proteins; Serum; surface antigens; surface proteins; Transmission-blocking; Vaccines; Virulence (Microbiology); Western blotting; zygote; Zygotes; China; Beijing China; United States > US; Transmission-blocking; Gamete; Plasmodium berghei; Fertilization; Ookinete
• ISSN: 1756-3305; 1756-3305
• DOI: 10.1186/s13071-022-05294-8

The Plasmodium zygote-to-ookinete developmental transition is an essential step for establishing an infection in the mosquito vector, and antigens expressed during this stage are potential targets for transmission-blocking vaccines (TBVs). The secreted ookinete protein 26 (PSOP26) is a newly identified ookinete surface protein. The anti-PSOP26 serum has moderate transmission-blocking activity, indicating the benefit of further investigating this protein as a target for TBVs. The function of psop26 was analyzed by targeted gene disruption. A chimeric PSOP25-PSOP26 protein was expressed in the Escherichia coli system. The PSOP25-PSOP26 fusion protein, along with mixed (PSOP25 + PSOP26) or single proteins (PSOP26 or PSOP25), were used for the immunization of mice. The antibody titers and immunogenicity of individual sera were analyzed by enzyme-linked immunoassay (ELISA), indirect immunofluorescence assay (IFA), and Western blot. The transmission-blocking activity of sera from different immunization schemes was assessed using in vitro and in vivo assays. PSOP26 is a surface protein expressed in Plasmodium gametes and ookinetes. The protein is dispensable for asexual blood-stage development, gametogenesis, and zygote formation, but is essential for the zygote-to-ookinete developmental transition. Specifically, both the prevalence of infections and oocyst densities were decreased in mosquitoes fed on psop26-null mutants. Mixtures of individual PSOP25 and PSOP26 fragments (PSOP25 + PSOP26), as well as chimeras (PSOP25-PSOP26), elicited high antibody levels in mice, with no immunological interference. Antisera against the mixed and fusion proteins elicited higher transmission-reducing activity (TRA) than antisera against the single PSOP26 antigen, but comparable to antisera against PSOP25 antigen alone. PSOP26 plays a critical role in the zygote-to-ookinete developmental transition. PSOP25 is a promising TBV candidate that could be used alone to target the ookinete stage.