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Sm‐p80‐based vaccine trial in baboons: efficacy when mimicking natural conditions of chronic disease, praziquantel therapy, immunization, and Schistosoma mansoni re‐encounter
Author(s) -
Siddiqui Arif J.,
Molehin Adebayo J.,
Zhang Weidong,
Ganapathy Pramodh K.,
Kim Eunjee,
Rojo Juan U.,
Redman Whitni K.,
Sennoune Souad R.,
Sudduth Justin,
Freeborn Jasmin,
Hunter Derick,
Kottapalli Kameswara R.,
Kottapalli Pratibha,
Wettashinghe Ruwanthi,
Dam Govert J.,
Corstjens Paul L.A.M.,
Papin James F.,
Carey David,
Torben Workineh,
Ahmad Gul,
Siddiqui Afzal A.
Publication year - 2018
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.13866
Subject(s) - praziquantel , baboon , biology , schistosoma mansoni , schistosomiasis , immunology , virology , schistosoma , vaccination , helminths , endocrinology
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.