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A genetically modified Plasmodium berghei parasite as a surrogate for whole-sporozoite vaccination against P. vivax malaria.
Moita, Diana; Maia, Teresa G; Duarte, Miguel; Andrade, Carolina M; Albuquerque, Inês S; Dwivedi, Ankit; Silva, Joana C; González-Céron, Lilia; Janse, Chris J; Mendes, António M; Prudêncio, Miguel.
Afiliación
  • Moita D; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
  • Maia TG; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
  • Duarte M; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
  • Andrade CM; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
  • Albuquerque IS; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
  • Dwivedi A; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Silva JC; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
  • González-Céron L; Centro Regional de Investigación en Salud Pública, Instituto Nacional de Salud Pública, Tapachula, Chiapas, México.
  • Janse CJ; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.
  • Mendes AM; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
  • Prudêncio M; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal. mprudencio@medicina.ulisboa.pt.
NPJ Vaccines ; 7(1): 163, 2022 Dec 16.
Article en En | MEDLINE | ID: mdl-36526627
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.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: NPJ Vaccines Año: 2022 Tipo del documento: Article País de afiliación: Portugal Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: NPJ Vaccines Año: 2022 Tipo del documento: Article País de afiliación: Portugal Pais de publicación: Reino Unido