Particle-based, Pfs230 and Pfs25 immunization is effective, but not improved by duplexing at fixed total antigen dose
Abstract Background The Plasmodium falciparum sexual-stage surface proteins Pfs25 and Pfs230 are antigen candidates for a malaria transmission-blocking vaccine (TBV), and have been widely investigated as such. It is not clear whether simultaneously presenting these two antigens in a particulate vacc...
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| Format: | Article |
| Language: | English |
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BMC
2020-08-01
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| Series: | Malaria Journal |
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| Online Access: | http://link.springer.com/article/10.1186/s12936-020-03368-5 |
| _version_ | 1819059573974106112 |
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| author | Wei-Chiao Huang Bingbing Deng Moustafa T. Mabrouk Amal Seffouh Joaquin Ortega Carole Long Kazutoyo Miura Yimin Wu Jonathan F. Lovell |
| author_facet | Wei-Chiao Huang Bingbing Deng Moustafa T. Mabrouk Amal Seffouh Joaquin Ortega Carole Long Kazutoyo Miura Yimin Wu Jonathan F. Lovell |
| author_sort | Wei-Chiao Huang |
| collection | DOAJ |
| description | Abstract Background The Plasmodium falciparum sexual-stage surface proteins Pfs25 and Pfs230 are antigen candidates for a malaria transmission-blocking vaccine (TBV), and have been widely investigated as such. It is not clear whether simultaneously presenting these two antigens in a particulate vaccine would enhance the transmission reducing activity (TRA) of induced antibodies. To assess this, immunization was carried out with liposomes containing synthetic lipid adjuvant monophosphoryl lipid A (MPLA), and cobalt-porphyrin-phospholipid (CoPoP), which rapidly converts recombinant, his-tagged antigens into particles. Methods His-tagged, recombinant Pfs25 and Pfs230C1 were mixed with CoPoP liposomes to form a bivalent vaccine. Antigens were fluorescently labelled to infer duplex particleization serum-stability and binding kinetics using fluorescence resonance energy transfer. Mice and rabbits were immunized with individual or duplexed particleized Pfs25 and Pfs230C1, at fixed total antigen doses. The resulting antibody responses were assessed for magnitude and TRA. Results Pfs230C1 and Pfs25 rapidly bound CoPoP liposomes to form a serum-stable, bivalent particle vaccine. In mice, immunization with 5 ng of total antigen (individual antigen or duplexed) elicited functional antibodies against Pfs25 and Pfs230. Compared to immunization with the individual antigen, Pfs25 antibody production was moderately lower for the bivalent CoPoP vaccine, whereas Pfs230C1 antibody production was not impacted. All antibodies demonstrated at least 92% inhibition in oocyst density at 750 μg/mL purified mouse IgG in the standard membrane feeding assay (SMFA). At lower IgG concentrations, the bivalent vaccine did not improve TRA; antibodies induced by particleized Pfs25 alone showed stronger function in these conditions. In rabbits, immunization with a 20 µg total antigen dose with the duplexed antigens yielded similar antibody production against Pfs25 and Pfs230 compared to immunization with a 20 µg dose of individual antigens. However, no enhanced TRA was observed with duplexing. Conclusions Pfs25, Pfs230 or the duplexed combination can readily be prepared as particulate vaccines by mixing CoPoP liposomes with soluble, recombinant antigens. This approach induces potent transmission-reducing antibodies following immunization in mice and rabbits. Immunization with bivalent, particleized, Pfs230 and Pfs25 did not yield antibodies with superior TRA compared to immunization with particleized Pfs25 as a single antigen. Altogether, duplexing antigens is straightforward and effective using CoPoP liposomes, but is likely to be more useful for targeting distinct parasite life stages. |
| first_indexed | 2024-12-21T14:13:15Z |
| format | Article |
| id | doaj.art-53505351d4854109a223735264100c34 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-21T14:13:15Z |
| publishDate | 2020-08-01 |
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| series | Malaria Journal |
| spelling | doaj.art-53505351d4854109a223735264100c342022-12-21T19:00:59ZengBMCMalaria Journal1475-28752020-08-0119111210.1186/s12936-020-03368-5Particle-based, Pfs230 and Pfs25 immunization is effective, but not improved by duplexing at fixed total antigen doseWei-Chiao Huang0Bingbing Deng1Moustafa T. Mabrouk2Amal Seffouh3Joaquin Ortega4Carole Long5Kazutoyo Miura6Yimin Wu7Jonathan F. Lovell8Department of Biomedical Engineering, University at Buffalo, State University of New YorkLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDepartment of Biomedical Engineering, University at Buffalo, State University of New YorkDepartment of Anatomy and Cell Biology, McGill University MontrealDepartment of Anatomy and Cell Biology, McGill University MontrealLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthPATH’s Malaria Vaccine Initiative (MVI)Department of Biomedical Engineering, University at Buffalo, State University of New YorkAbstract Background The Plasmodium falciparum sexual-stage surface proteins Pfs25 and Pfs230 are antigen candidates for a malaria transmission-blocking vaccine (TBV), and have been widely investigated as such. It is not clear whether simultaneously presenting these two antigens in a particulate vaccine would enhance the transmission reducing activity (TRA) of induced antibodies. To assess this, immunization was carried out with liposomes containing synthetic lipid adjuvant monophosphoryl lipid A (MPLA), and cobalt-porphyrin-phospholipid (CoPoP), which rapidly converts recombinant, his-tagged antigens into particles. Methods His-tagged, recombinant Pfs25 and Pfs230C1 were mixed with CoPoP liposomes to form a bivalent vaccine. Antigens were fluorescently labelled to infer duplex particleization serum-stability and binding kinetics using fluorescence resonance energy transfer. Mice and rabbits were immunized with individual or duplexed particleized Pfs25 and Pfs230C1, at fixed total antigen doses. The resulting antibody responses were assessed for magnitude and TRA. Results Pfs230C1 and Pfs25 rapidly bound CoPoP liposomes to form a serum-stable, bivalent particle vaccine. In mice, immunization with 5 ng of total antigen (individual antigen or duplexed) elicited functional antibodies against Pfs25 and Pfs230. Compared to immunization with the individual antigen, Pfs25 antibody production was moderately lower for the bivalent CoPoP vaccine, whereas Pfs230C1 antibody production was not impacted. All antibodies demonstrated at least 92% inhibition in oocyst density at 750 μg/mL purified mouse IgG in the standard membrane feeding assay (SMFA). At lower IgG concentrations, the bivalent vaccine did not improve TRA; antibodies induced by particleized Pfs25 alone showed stronger function in these conditions. In rabbits, immunization with a 20 µg total antigen dose with the duplexed antigens yielded similar antibody production against Pfs25 and Pfs230 compared to immunization with a 20 µg dose of individual antigens. However, no enhanced TRA was observed with duplexing. Conclusions Pfs25, Pfs230 or the duplexed combination can readily be prepared as particulate vaccines by mixing CoPoP liposomes with soluble, recombinant antigens. This approach induces potent transmission-reducing antibodies following immunization in mice and rabbits. Immunization with bivalent, particleized, Pfs230 and Pfs25 did not yield antibodies with superior TRA compared to immunization with particleized Pfs25 as a single antigen. Altogether, duplexing antigens is straightforward and effective using CoPoP liposomes, but is likely to be more useful for targeting distinct parasite life stages.http://link.springer.com/article/10.1186/s12936-020-03368-5Pfs25Pfs230MalariaTransmission-blocking vaccineLiposomes |
| spellingShingle | Wei-Chiao Huang Bingbing Deng Moustafa T. Mabrouk Amal Seffouh Joaquin Ortega Carole Long Kazutoyo Miura Yimin Wu Jonathan F. Lovell Particle-based, Pfs230 and Pfs25 immunization is effective, but not improved by duplexing at fixed total antigen dose Malaria Journal Pfs25 Pfs230 Malaria Transmission-blocking vaccine Liposomes |
| title | Particle-based, Pfs230 and Pfs25 immunization is effective, but not improved by duplexing at fixed total antigen dose |
| title_full | Particle-based, Pfs230 and Pfs25 immunization is effective, but not improved by duplexing at fixed total antigen dose |
| title_fullStr | Particle-based, Pfs230 and Pfs25 immunization is effective, but not improved by duplexing at fixed total antigen dose |
| title_full_unstemmed | Particle-based, Pfs230 and Pfs25 immunization is effective, but not improved by duplexing at fixed total antigen dose |
| title_short | Particle-based, Pfs230 and Pfs25 immunization is effective, but not improved by duplexing at fixed total antigen dose |
| title_sort | particle based pfs230 and pfs25 immunization is effective but not improved by duplexing at fixed total antigen dose |
| topic | Pfs25 Pfs230 Malaria Transmission-blocking vaccine Liposomes |
| url | http://link.springer.com/article/10.1186/s12936-020-03368-5 |
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