Characterization of PSOP26 as an ookinete surface antigen with improved transmission-blocking activity when fused with PSOP25
Abstract Background 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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | Parasites & Vectors |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13071-022-05294-8 |
| _version_ | 1811324509669556224 |
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| author | Peng-peng Wang Xuefeng Jiang Jie Bai Fan Yang Xinxin Yu Yudi Wu Wenqi Zheng Yongzhe Zhang Liwang Cui Fei Liu Xiaotong Zhu Yaming Cao |
| author_facet | Peng-peng Wang Xuefeng Jiang Jie Bai Fan Yang Xinxin Yu Yudi Wu Wenqi Zheng Yongzhe Zhang Liwang Cui Fei Liu Xiaotong Zhu Yaming Cao |
| author_sort | Peng-peng Wang |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. |
| first_indexed | 2024-04-13T14:15:37Z |
| format | Article |
| id | doaj.art-a8bfdfeb4b4841d9b938b9e720ef4faa |
| institution | Directory Open Access Journal |
| issn | 1756-3305 |
| language | English |
| last_indexed | 2024-04-13T14:15:37Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Parasites & Vectors |
| spelling | doaj.art-a8bfdfeb4b4841d9b938b9e720ef4faa2022-12-22T02:43:39ZengBMCParasites & Vectors1756-33052022-05-0115111410.1186/s13071-022-05294-8Characterization of PSOP26 as an ookinete surface antigen with improved transmission-blocking activity when fused with PSOP25Peng-peng Wang0Xuefeng Jiang1Jie Bai2Fan Yang3Xinxin Yu4Yudi Wu5Wenqi Zheng6Yongzhe Zhang7Liwang Cui8Fei Liu9Xiaotong Zhu10Yaming Cao11Department of Immunology, College of Basic Medical Sciences, China Medical UniversityDepartment of Immunology, College of Basic Medical Sciences, China Medical UniversityDepartment of Immunology, College of Basic Medical Sciences, China Medical UniversityDepartment of Immunology, College of Basic Medical Sciences, China Medical UniversityDepartment of Immunology, College of Basic Medical Sciences, China Medical UniversityDepartment of Immunology, College of Basic Medical Sciences, China Medical UniversityDepartment of Clinical Laboratory, Affiliated Hospital of Inner Mongolian Medical UniversityDepartment of Pathogen Biology, College of Basic Medical Sciences, China Medical UniversityDepartment of Internal Medicine, Morsani College of Medicine, University of South FloridaDepartment of Immunology, College of Basic Medical Sciences, China Medical UniversityDepartment of Immunology, College of Basic Medical Sciences, China Medical UniversityDepartment of Immunology, College of Basic Medical Sciences, China Medical UniversityAbstract Background 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. Methods 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. Results 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. Conclusions 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.https://doi.org/10.1186/s13071-022-05294-8Plasmodium bergheiGameteOokineteFertilizationTransmission-blocking |
| spellingShingle | Peng-peng Wang Xuefeng Jiang Jie Bai Fan Yang Xinxin Yu Yudi Wu Wenqi Zheng Yongzhe Zhang Liwang Cui Fei Liu Xiaotong Zhu Yaming Cao Characterization of PSOP26 as an ookinete surface antigen with improved transmission-blocking activity when fused with PSOP25 Parasites & Vectors Plasmodium berghei Gamete Ookinete Fertilization Transmission-blocking |
| title | Characterization of PSOP26 as an ookinete surface antigen with improved transmission-blocking activity when fused with PSOP25 |
| title_full | Characterization of PSOP26 as an ookinete surface antigen with improved transmission-blocking activity when fused with PSOP25 |
| title_fullStr | Characterization of PSOP26 as an ookinete surface antigen with improved transmission-blocking activity when fused with PSOP25 |
| title_full_unstemmed | Characterization of PSOP26 as an ookinete surface antigen with improved transmission-blocking activity when fused with PSOP25 |
| title_short | Characterization of PSOP26 as an ookinete surface antigen with improved transmission-blocking activity when fused with PSOP25 |
| title_sort | characterization of psop26 as an ookinete surface antigen with improved transmission blocking activity when fused with psop25 |
| topic | Plasmodium berghei Gamete Ookinete Fertilization Transmission-blocking |
| url | https://doi.org/10.1186/s13071-022-05294-8 |
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