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Ann N Y Acad Sci ; 1425(1): 19-37, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29888790

RESUMO

Sm-p80-based vaccine efficacy for Schistosoma mansoni was evaluated in a baboon model of infection and disease. The study was designed to replicate a human vaccine implementation scenario for endemic regions in which vaccine would be administered following drug treatment of infected individuals. In our study, the Sm-p80-based vaccine reduced principal pathology producing hepatic egg burdens by 38.0% and egg load in small and large intestines by 72.2% and 49.4%, respectively, in baboons. Notably, hatching rates of eggs recovered from liver and small and large intestine of vaccinated animals were significantly reduced, by 60.4%, 48.6%, and 82.3%, respectively. Observed reduction in egg maturation/hatching rates was supported by immunofluorescence and confocal microscopy showing unique differences in Sm-p80 expression in worms of both sexes and matured eggs. Vaccinated baboons had a 64.5% reduction in urine schistosome circulating anodic antigen, a parameter that reflects worm numbers/health status in infected hosts. Preliminary analyses of RNA sequencing revealed unique genes and canonical pathways associated with establishment of chronic disease, praziquantel-mediated parasite killing, and Sm-p80-mediated protection in vaccinated baboons. Overall, our study demonstrated efficacy of the Sm-p80 vaccine and provides insight into some of the epistatic interactions associated with protection.


Assuntos
Praziquantel/uso terapêutico , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Vacinação/métodos , Vacinas/imunologia , Animais , Anti-Helmínticos/uso terapêutico , Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/imunologia , Doença Crônica , Feminino , Humanos , Masculino , Contagem de Ovos de Parasitas , Schistosoma mansoni/efeitos dos fármacos , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/terapia , Resultado do Tratamento , Vacinas/administração & dosagem
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