Vaccine Efficacy against Malaria by the Combination of Porcine Parvovirus-Like Particles and Vaccinia Virus Vectors Expressing CS of PlasmodiumReportar como inadecuado




Vaccine Efficacy against Malaria by the Combination of Porcine Parvovirus-Like Particles and Vaccinia Virus Vectors Expressing CS of Plasmodium - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

With the aim to develop an efficient and cost-effective approach to control malaria, we have generated porcine parvovirus-like particles PPV-VLPs carrying the CD8+ T cell epitope SYVPSAEQI of the circumsporozoite CS protein from Plasmodium yoelii fused to the PPV VP2 capsid protein PPV-PYCS, and tested in prime-boost protocols with poxvirus vectors for efficacy in a rodent malaria model. As a proof-of concept, we have characterized the anti-CS CD8+ T cell response elicited by these hybrid PPV-VLPs in BALB-c mice after immunizations with the protein PPV-PYCS administered alone or in combination with recombinant vaccinia virus VACV vectors from the Western Reserve WR and modified virus Ankara MVA strains expressing the entire P. yoelii CS protein. The results of different immunization protocols showed that the combination of PPV-PYCS prime-poxvirus boost was highly immunogenic, inducing specific CD8+ T cell responses to CS resulting in 95% reduction in liver stage parasites two days following sporozoite challenge. In contrast, neither the administration of PPV-PYCS alone nor the immunization with the vectors given in the order poxvirus-VLPs was as effective. The immune profile induced by VLPs-MVA boost was associated with polyfunctional and effector memory CD8+ T cell responses. These findings highlight the use of recombinant parvovirus PPV-PYCS particles as priming agents and poxvirus vectors, like MVA, as booster to enhance specific CD8+ T cell responses to Plasmodium antigens and to control infection. These observations are relevant in the design of T cell-inducing vaccines against malaria.



Autor: Dolores Rodríguez, Gloria González-Aseguinolaza, Juan R. Rodríguez, Aneesh Vijayan, Magdalena Gherardi, Paloma Rueda, J. Ignac

Fuente: http://plos.srce.hr/



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