Fifteen Years of Sm-p80-Based Vaccine Trials in Nonhuman Primates: Antibodies From Vaccinated Baboons Confer Protection in vivo and in vitro From Schistosoma mansoni and Identification of Putative Correlative Markers of Protection.

Weidong Zhang,Adebayo J Molehin,David Carey,Sabiha Khatoon,Darrick Carter,Juan U Rojo,Souvik Karmakar,Ashraf F Rezk,Roman F Wolf,Samara Lazarus,Workineh Torben,Ray Damian,Florian Marks,Justin Sudduth,Sean A Gray,James F Papin,Afzal A Siddiqui,Jasmin Freeborn,Gufran Ahmad ,Souad R Sennoune ,Arif Jamal Siddiqui ,Liu Le

doi:10.3389/fimmu.2020.01246

Abstract

Recent advances in systems biology have shifted vaccine development from a largely trial-and-error approach to an approach that promote rational design through the search for immune signatures and predictive correlates of protection. These advances will doubtlessly accelerate the development of a vaccine for schistosomiasis, a neglected tropical disease that currently affects over 250 million people. For over 15 years and with contributions of over 120 people, we have endeavored to test and optimize Sm-p80-based vaccines in the non-human primate model of schistosomiasis. Using RNA-sequencing on eight different Sm-p80-based vaccine strategies, we sought to elucidate immune signatures correlated with experimental protective efficacy. Furthermore, we aimed to explore the role of antibodies through in vivo passive transfer of IgG obtained from immunized baboons and in vitro killing of schistosomula using Sm-p80-specific antibodies. We report that passive transfer of IgG from Sm-p80-immunized baboons led to significant worm burden reduction, egg reduction in liver, and reduced egg hatching percentages from tissues in mice compared to controls. In addition, we observed that sera from Sm-p80-immunized baboons were able to kill a significant percent of schistosomula and that this effect was complement-dependent. While we did not find a universal signature of immunity, the large datasets generated by this study will serve as a substantial resource for further efforts to develop vaccine or therapeutics for schistosomiasis.

Highlights

IntroductionWhile the rate of mortality is relatively low considering over 250 million people live with this disease [2], the clinical manifestations of schistosomiasis are chronic and insidious, including anemia, growth retardation, fever, genital lesions, hepatosplenomegaly and slow, irreversible organ damage [3, 4]
Schistosomiasis is a debilitating neglected tropical disease caused by infection with parasitic trematodes of the genus Schistosoma
Our results showed a significant schistosomula killing when cultured in the presence of sera obtained from Sm-p80vaccinated baboons when compared to sera from control baboons and the killing effect was significantly augmented with the addition of exogenous complement

Summary

Introduction

While the rate of mortality is relatively low considering over 250 million people live with this disease [2], the clinical manifestations of schistosomiasis are chronic and insidious, including anemia, growth retardation, fever, genital lesions, hepatosplenomegaly and slow, irreversible organ damage [3, 4]. While some success in reducing the spread of this disease have been achieved through integrated approaches combining mass drug administration (MDA), molluscicides, health education, behavior modification, and public works programs such as construction of concrete irrigation canals, schistosomiasis continues to be a major source of global health burden [7,8,9] Implementation of these integrated interventions can be logistical questions in economically strained communities such as rural villages in sub-Saharan Africa and southeast Asia [10, 11]. Development of an antischistosome vaccine would be beneficial to achieve schistosomiasis elimination goals [17,18,19]

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