Abstract
Schistosomiasis is an important parasitic disease worldwide that affects more than 207 million people in 76 countries and causes approximately 250,000 deaths per year. The best long-term strategy to control schistosomiasis is through immunization combined with drug treatment. Due to the ability of DNA vaccines to generate humoral and cellular immune responses, such vaccines are considered a promising approach against schistosomiasis. Sm29 and tetraspanin-2 (Sm-TSP2) are two proteins that are located in the S. mansoni tegument of adult worms and schistosomula and induce high levels of protection through recombinant protein immunization. In this study, we transfected BHK-21 cells with plasmids encoding Sm29, Sm-TSP2 or a chimera containing both genes. Using RT-PCR analysis and western blot, we confirmed that the DNA vaccine constructs were transcribed and translated, respectively, in BHK-21 cells. After immunization of mice, we evaluated the reduction in worm burden. We observed worm burden reductions of 17-22%, 22%, 31-32% and 24-32% in animals immunized with the pUMVC3/Sm29, pUMVC3/SmTSP-2, pUMVC3/Chimera and pUMVC3/Sm29 + pUMVC3/SmTSP-2 plasmids, respectively. We evaluated the humoral response elicited by DNA vaccines, and animals immunized with pUMVC3/Sm29 and pUMVC3/Sm29 + pUMVC3/SmTSP-2 showed higher titers of anti-Sm29 antibodies. The cytokine profile produced by the spleen cells of immunized mice was then evaluated. We observed higher production of Th1 cytokines, such as TNF-α and IFN-γ, in vaccinated mice and no significant production of IL-4 and IL-5. The DNA vaccines tested in this study showed the ability to generate a protective immune response against schistosomiasis, probably through the production of Th1 cytokines. However, future strategies aiming to optimize the protective response induced by a chimeric DNA construct need to be developed.
Highlights
Schistosomiasis is an important parasitic disease that affects approximately 207 million people in 76 countries worldwide, of which 120 million are symptomatic and 20 million develop the severe form of the disease [1]
The DNA vaccine constructs used in immunization experiments were analyzed for mRNA and protein expression levels in Baby Hamster Kidney-21 (BHK-21) cells. mRNA expression was determined by real time RT-PCR analysis using specific primers for Sm29, Sm29 and tetraspanin-2 (SmTSP-2) and for a specific region of the chimera
Significant levels of SmTSP-2 mRNA were observed in extracts of pUMVC3/chimera or the control (pUMVC3)/SmTSP2 and pUMVC3/chimera transfected cells compared to the controls (Fig 1B)
Summary
Schistosomiasis is an important parasitic disease that affects approximately 207 million people in 76 countries worldwide, of which 120 million are symptomatic and 20 million develop the severe form of the disease [1]. Many investigators believe that a prophylactic vaccination would be an ideal approach either alone or together with chemotherapy, which can be effective in the reduction of morbidity and transmission of schistosomiasis [4,5]. A vaccine that induces even a partial reduction in worm burden could considerably reduce pathology and limit parasite transmission [6,7]. DNA vaccines have the potential to induce innate and adaptive immune systems, are easy to manufacture and distribute and are stable at room temperature and apparently safe for human use, which are considered by many to be ideal characteristics of an effective vaccine against schistosomiasis [9,10,11,12,13,14]. Some DNA vaccines have already been tested against S. mansoni, and several of them have achieved significant levels of protection, such as Sm-p80, Sm23 and Cu/Zn superoxide dismutase, which showed 59%, 25– 44% and 44–60% worm burden reduction, respectively [15,16,17]
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