Protective Effects of Membrane-Anchored and Secreted DNA Vaccines Encoding Fatty Acid-Binding Protein and Glutathione S-Transferase against Schistosoma japonicum

Yaqin Tu,Wuxing Dai,Guorun Fan,Yin Zhang,Chengwu Tang,Zhihao Chen,Yang Hu,Dandan Man,Shuojie Liu,Lin Liu,Geoffrey N Gobert

doi:10.1371/journal.pone.0086575

Abstract

In order to explore the high performance bivalent DNA-based vaccine against schistosomes, SjFABP and Sj26GST were selected and used to construct a vaccine. Two strategies were used to construct the bivalent DNA vaccine. In the first strategy, a plasmid encoding antigen in the secreted form was used, while in the other, a plasmid encoding a truncated form of SjFABP and Sj26GST targeted to the cell surface was used. Various parameters, including antibody and cytokine response, proliferation, histopathological examination, and characterization of T cell subsets were used to evaluate the type of immune response and the level of protection against challenge infection. Injection with secreted pIRES-sjFABP-sj26GST significantly increased the levels of antibody, splenocyte proliferation, and production of IFN-γ, compared with membrane-anchored groups. Analysis of splenic T cell subsets showed that the secreted vaccine significantly increased the percentage of CD3+CD4+ and CD3+CD8+ T cells. Liver immunopathology (size of liver granulomas) was significantly reduced in the secreted group compared with the membrane-anchored groups. Moreover, challenge experiments showed that the worm and egg burdens were significantly reduced in animals immunized with recombinant vaccines. Most importantly, secreted Sj26GST-SjFABP markedly enhanced protection, by reducing worm and egg burdens by 31.8% and 24.78%, respectively, while the membrane-anchored group decreased worm and egg burdens by 24.80% and 18.80%, respectively. Taken together, these findings suggest that the secretory vaccine is more promising than the membrane-anchored vaccine, and provides support for the development and application of this vaccine.

Highlights

Schistosomiasis, a tropical disease that is caused by Schistosoma japonicum, is the most endemic and zoonotic disease in China, causing morbidity and mortality in almost 90 counties and affecting around 59 million individuals [1]
Vaccination with membrane-anchored or secreted pIRES-sjFABP-sj26GST induced significant and progressive increases in total IgG responses against Soluble worm antigen preparation (SWAP) (P,0.05), compared with the control group injected with pIRES
No studies have been conducted to compare the immunogenicity between vaccines encoding secretory and membrane-anchored proteins in terms of S. japonicum

Summary

Introduction

Schistosomiasis, a tropical disease that is caused by Schistosoma japonicum, is the most endemic and zoonotic disease in China, causing morbidity and mortality in almost 90 counties and affecting around 59 million individuals [1]. DNA vaccines are promising when compared to other types of vaccines such as attenuated, subunit, and genetically engineered vaccines. They have low cost of production and high thermal stability, and are convenient to store. The World Health Organization (WHO) has recommended 6 major antigens, including membrane proteins, muscle components, and enzymes, as candidates for a more potent DNA vaccine for schistosomiasis. Among these antigens, the fatty acid-binding protein FABP (SjFABP) and glutathione S-transferase GST (Sj26GST) were shown to induce protective immunity in several laboratory studies [2,3,4]. Multivalent DNA vaccines produce a variety of antigens with a large number of epitopes that can elicit a robust immune reaction, making them more potent and effective

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Conclusion