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

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.

Oral Vaccination with Attenuated Salmonella typhimurium-Delivered TsPmy DNA Vaccine Elicits Protective Immunity against Trichinella spiralis in BALB/c Mice

“…DNA vaccine is considered an alternative, even optimal approach because of the simplicity of its manufacturing and distribution, biological stability and cost effectiveness [ 31 ]. DNA vaccines have been shown to induce protective immunity against abroad range of pathogens such as Dengue virus [ 32 ], intracellular protozoan Leishmania major [ 33 ] or helminth parasite Schistosoma japonicum [ 34 ]. DNA vaccine contains a eukaryotic expression vector that could improve protein folding, therefore enable surface-exposed epitopes to be correctly presented and enable post-translational modification [ 35 ].…”

Schistosomiasis vaccines: where do we stand?

“…The latter study also showed that SjFABP + IL-18 increased the Th1 immune response by producing a higher level of IFNγ and a lower level of IL-4 compared with mice vaccinated only with SjFABP [ 80 ]. Somewhat disappointedly, the Sj14 DNA vaccine, coupled with Sj26GST to form a bivalent DNA-based vaccine, resulted in a reduced level of protective efficacy [ 81 ].…”

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

“…To date, several S. japonicum vaccine candidates have been tried [reviewed in Tebeje et al ( 20 )] including a 67 kDa S. japonicum surface protein (Sj67) ( 21 ), the Triose Phosphate Isomerase (SjTPI) ( 22 , 23 ), a Thyroid hormone receptor beta (SjTHRβ) ( 24 ), a S. japonicum fatty acid binding protein (SjFABP) ( 25 , 26 ), a 23-kDa tetraspanin protein (rSjC23DNA) fused to bovine heat shock protein 70 (HSP70) ( 27 ), a 26-kDa parenchymal protein (Sj26GST) ( 28 ), and the 97-kDa protein Paramyosin (Sj97) ( 12 , 29 – 31 ). Several of these, particularly rSJC23DNA, Paramyosin, and SjTPI have shown promise in preliminary protection studies in water buffalo.…”