Abstract
BackgroundSchistosomiasis is one of the most important neglected diseases found in developing countries and affects 249 million people worldwide. The development of an efficient vaccination strategy is essential for the control of this disease. Previous work showed partial protection induced by DNA-Sm14 against Schistosoma mansoni infection, whereas DNA-Hsp65 showed immunostimulatory properties against infectious diseases, autoimmune diseases, cancer and antifibrotic properties in an egg-induced granuloma model.MethodsC57BL/6 mice received 4 doses of DNA-Sm14 (100 μg/dose) and DNA-Hsp65 (100 μg/dose), simultaneously administrated, or DNA-Sm14 alone, once a week, during four weeks. Three groups were included: 1- Control (no immunization); 2- DNA-Sm14; 3- DNA-Sm14/DNA-Hsp65. Two weeks following last immunization, animals were challenged subcutaneously with 30 cercariae. Fifteen, 48 and 69 days after infection splenocytes were collected to evaluate the number of CD8+ memory T cells (CD44highCD62low) using flow cytometry. Forty-eight days after challenge adult worms were collected by portal veins perfusion and intestines were collected to analyze the intestinal egg viability. Histological, immunohistochemical and soluble quantification of collagen and α-SMA accumulation were performed on the liver.ResultsIn the current work, we tested a new vaccination strategy using DNA-Sm14 with DNA-Hsp65 to potentiate the protection against schistosomiasis. Combined vaccination increased the number of CD8+ memory T cells and decreased egg viability on the intestinal wall of infected mice. In addition, simultaneous vaccination with DNA-Sm14/DNA-Hsp65 reduced collagen and α-SMA accumulation during the chronic phase of granuloma formation.ConclusionSimultaneous vaccination with DNA-Sm14/DNA-Hsp65 showed an immunostimulatory potential and antifibrotic property that is associated with the reduction of tissue damage on Schistosoma mansoni experimental infection.
Highlights
Schistosomiasis is one of the most important neglected diseases found in developing countries and affects 249 million people worldwide
To determine the impact of DNA-Sm14 and DNA-Sm14/DNA-Hsp65 on the generation of memory T cells, we assessed the frequencies of CD4+ and CD8+ memory T lymphocytes in the spleen of mice infected with S. mansoni
Vaccination with DNA-Sm14 or DNA-Sm14/DNA-Hsp65 increased the number of CD8+ CD44hiCD62Llow cells 48 and 69 days post infection (Figure 1A)
Summary
Schistosomiasis is one of the most important neglected diseases found in developing countries and affects 249 million people worldwide. Schistosomiasis is one of the most important neglected diseases found in developing countries and constitutes a serious public health problem that is directly related to poverty and social disadvantage [1,2]. This disease affects 249 million people worldwide [3]. Given the immunostimulatory and protective potential of DNA-Sm14 in the prevention against schistosomiasis, new strategies that complement and modulate the immune response generated by DNASm14 are important to achieve satisfactory protection levels
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