Process Development of Sj-p80: A Low-Cost Transmission-Blocking Veterinary Vaccine for Asiatic Schistosomiasis.

Adebayo J Molehin,Christopher Peterson,Afzal A Siddiqui,Cheri Turner,Sabiha Khatoon,Madison Rattan,Sean A Gray,Darrick Carter,Souad R Sennoune,Rebecca Kernen,Jennifer Davis,Weidong Zhang

doi:10.3389/fimmu.2020.578715

Abstract

Asiatic schistosomiasis caused by Schistosoma japonicum is a neglected tropical disease resulting in significant morbidity to both humans and animals - particularly bovines - in endemic areas. Infection with this parasite leads to less healthy herds, causing problems in communities which rely on bovines for farming, milk and meat production. Additionally, excretion of parasite eggs in feces perpetuates the life cycle and can lead to human infection. We endeavored to develop a minimally purified, inexpensive, and effective vaccine based on the 80 kDa large subunit of the calcium activated neutral protease (calpain) from S. japonicum (Sj-p80). Here we describe the production of veterinary vaccine-grade Sj-p80 at four levels of purity and demonstrate in a pilot study that minimally purified antigen provides protection against infection in mice when paired with a low-cost veterinary adjuvant, Montanide™ ISA61 VG. Preliminary data demonstrate that the vaccine is immunogenic with robust antibody titers following immunization, and vaccination resulted in a reduction of parasite eggs being deposited in the liver (23.4–51.4%) and intestines (1.9–55.1%) depending on antigen purity as well as reducing the ability of these eggs to hatch into miracidia by up to 31.6%. We therefore present Sj-p80 as a candidate vaccine antigen for Asiatic schistosomiasis which is now primed for continued development and testing in bovines in endemic areas. A successful bovine vaccine could play a major role in reducing pathogen transmission to humans by interrupting the parasitic life cycle and improving quality of life for people living in endemic countries.

Highlights

Schistosomiasis remains a major parasitic disease of global health importance
Our preliminary studies suggest that Sj-p80 may emerge as a viable vaccine candidate for Asiatic schistosomiasis, either alone or possibly in combination with other promising candidates, once protection is demonstrated in bovines
Expression scouting at temperatures ranging from 15°C to 37°C all resulted in the Sj-p80 protein being localized entirely into inclusion bodies (IB)

Summary

Introduction

Schistosomiasis remains a major parasitic disease of global health importance. The disease is caused by infection with one of several parasitic trematodes belonging to the genus Schistosoma. The three most important species are S. mansoni, S. japonicum and S. haematobium, each which cause clinically distinct diseases. Over the last few decades, schistosomiasis control programs have largely been predicated on mass administration of the drug praziquantel (PZQ) with water, sanitation and hygiene (WASH) programs serving as adjuncts. Despite these large-scale control programs, the prevalence and transmission of schistosomiasis have remained largely unchecked while the disease is gaining foothold in geographical areas previously schistosomiasis-free due to the formation of hybrid parasites from bovine- and human-tropic species [7,8,9,10], increasing the urgency to address veterinary schistosomiasis

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Results

Conclusion