A genetically modified Plasmodium berghei parasite as a surrogate for whole-sporozoite vaccination against P. vivax malaria
Abstract Two malaria parasite species, Plasmodium falciparum (Pf) and P. vivax (Pv) are responsible for most of the disease burden caused by malaria. Vaccine development against this disease has focused mainly on Pf. Whole-sporozoite (WSp) vaccination, targeting pre-erythrocytic (PE) parasite stages...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-12-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-022-00585-8 |
| _version_ | 1797429318416072704 |
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| author | Diana Moita Teresa G. Maia Miguel Duarte Carolina M. Andrade Inês S. Albuquerque Ankit Dwivedi Joana C. Silva Lilia González-Céron Chris J. Janse António M. Mendes Miguel Prudêncio |
| author_facet | Diana Moita Teresa G. Maia Miguel Duarte Carolina M. Andrade Inês S. Albuquerque Ankit Dwivedi Joana C. Silva Lilia González-Céron Chris J. Janse António M. Mendes Miguel Prudêncio |
| author_sort | Diana Moita |
| collection | DOAJ |
| description | Abstract Two malaria parasite species, Plasmodium falciparum (Pf) and P. vivax (Pv) are responsible for most of the disease burden caused by malaria. Vaccine development against this disease has focused mainly on Pf. Whole-sporozoite (WSp) vaccination, targeting pre-erythrocytic (PE) parasite stages, is a promising strategy for immunization against malaria and several PfWSp-based vaccine candidates are currently undergoing clinical evaluation. In contrast, no WSp candidates have been developed for Pv, mainly due to constraints in the production of Pv sporozoites in the laboratory. Recently, we developed a novel approach for WSp vaccination against Pf based on the use of transgenic rodent P. berghei (Pb) sporozoites expressing immunogens of this human-infective parasite. We showed that this platform can be used to deliver PE Pf antigens, eliciting both targeted humoral responses and cross-species cellular immune responses against Pf. Here we explored this WSp platform for the delivery of Pv antigens. As the Pv circumsporozoite protein (CSP) is a leading vaccine candidate antigen, we generated a transgenic Pb parasite, PbviVac, that, in addition to its endogenous PbCSP, expresses PvCSP under the control of a strictly PE promoter. Immunofluorescence microscopy analyses confirmed that both the PbCSP and the PvCSP antigens are expressed in PbviVac sporozoites and liver stages and that PbviVac sporozoite infectivity of hepatic cells is similar to that of its wild-type Pb counterpart. Immunization of mice with PbviVac sporozoites elicits the production of anti-PvCSP antibodies that efficiently recognize and bind to Pv sporozoites. Our results warrant further development and evaluation of PbviVac as a surrogate for WSp vaccination against Pv malaria. |
| first_indexed | 2024-03-09T09:11:27Z |
| format | Article |
| id | doaj.art-e826d5ba7493466aa874bf76000cc79f |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-09T09:11:27Z |
| publishDate | 2022-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-e826d5ba7493466aa874bf76000cc79f2023-12-02T08:37:33ZengNature Portfolionpj Vaccines2059-01052022-12-01711910.1038/s41541-022-00585-8A genetically modified Plasmodium berghei parasite as a surrogate for whole-sporozoite vaccination against P. vivax malariaDiana Moita0Teresa G. Maia1Miguel Duarte2Carolina M. Andrade3Inês S. Albuquerque4Ankit Dwivedi5Joana C. Silva6Lilia González-Céron7Chris J. Janse8António M. Mendes9Miguel Prudêncio10Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de LisboaInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de LisboaInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de LisboaInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de LisboaInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de LisboaInstitute for Genome Sciences, University of Maryland School of MedicineInstitute for Genome Sciences, University of Maryland School of MedicineCentro Regional de Investigación en Salud Pública, Instituto Nacional de Salud PúblicaDepartment of Parasitology, Leiden University Medical CenterInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de LisboaInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de LisboaAbstract Two malaria parasite species, Plasmodium falciparum (Pf) and P. vivax (Pv) are responsible for most of the disease burden caused by malaria. Vaccine development against this disease has focused mainly on Pf. Whole-sporozoite (WSp) vaccination, targeting pre-erythrocytic (PE) parasite stages, is a promising strategy for immunization against malaria and several PfWSp-based vaccine candidates are currently undergoing clinical evaluation. In contrast, no WSp candidates have been developed for Pv, mainly due to constraints in the production of Pv sporozoites in the laboratory. Recently, we developed a novel approach for WSp vaccination against Pf based on the use of transgenic rodent P. berghei (Pb) sporozoites expressing immunogens of this human-infective parasite. We showed that this platform can be used to deliver PE Pf antigens, eliciting both targeted humoral responses and cross-species cellular immune responses against Pf. Here we explored this WSp platform for the delivery of Pv antigens. As the Pv circumsporozoite protein (CSP) is a leading vaccine candidate antigen, we generated a transgenic Pb parasite, PbviVac, that, in addition to its endogenous PbCSP, expresses PvCSP under the control of a strictly PE promoter. Immunofluorescence microscopy analyses confirmed that both the PbCSP and the PvCSP antigens are expressed in PbviVac sporozoites and liver stages and that PbviVac sporozoite infectivity of hepatic cells is similar to that of its wild-type Pb counterpart. Immunization of mice with PbviVac sporozoites elicits the production of anti-PvCSP antibodies that efficiently recognize and bind to Pv sporozoites. Our results warrant further development and evaluation of PbviVac as a surrogate for WSp vaccination against Pv malaria.https://doi.org/10.1038/s41541-022-00585-8 |
| spellingShingle | Diana Moita Teresa G. Maia Miguel Duarte Carolina M. Andrade Inês S. Albuquerque Ankit Dwivedi Joana C. Silva Lilia González-Céron Chris J. Janse António M. Mendes Miguel Prudêncio A genetically modified Plasmodium berghei parasite as a surrogate for whole-sporozoite vaccination against P. vivax malaria npj Vaccines |
| title | A genetically modified Plasmodium berghei parasite as a surrogate for whole-sporozoite vaccination against P. vivax malaria |
| title_full | A genetically modified Plasmodium berghei parasite as a surrogate for whole-sporozoite vaccination against P. vivax malaria |
| title_fullStr | A genetically modified Plasmodium berghei parasite as a surrogate for whole-sporozoite vaccination against P. vivax malaria |
| title_full_unstemmed | A genetically modified Plasmodium berghei parasite as a surrogate for whole-sporozoite vaccination against P. vivax malaria |
| title_short | A genetically modified Plasmodium berghei parasite as a surrogate for whole-sporozoite vaccination against P. vivax malaria |
| title_sort | genetically modified plasmodium berghei parasite as a surrogate for whole sporozoite vaccination against p vivax malaria |
| url | https://doi.org/10.1038/s41541-022-00585-8 |
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