Sm-p80-based vaccine trial in baboons: efficacy when mimicking natural conditions of chronic disease, praziquantel therapy, immunization, and Schistosoma mansoni re-encounter.

Abstract:

: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.

journal_name

Ann N Y Acad Sci

authors

Siddiqui AJ,Molehin AJ,Zhang W,Ganapathy PK,Kim E,Rojo JU,Redman WK,Sennoune SR,Sudduth J,Freeborn J,Hunter D,Kottapalli KR,Kottapalli P,Wettashinghe R,van Dam GJ,Corstjens PLAM,Papin JF,Carey D,Torben W,Ahmad G,S

doi

10.1111/nyas.13866

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

19-37

issue

1

eissn

0077-8923

issn

1749-6632

journal_volume

1425

pub_type

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