Combined immunization using DNA-Sm14 and DNA-Hsp65 increases CD8+ memory T cells, reduces chronic pathology and decreases egg viability during Schistosoma mansoniinfection

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.

Development of Urinary Bladder Pre-Neoplasia by Schistosoma haematobium Eggs and Chemical Carcinogen in Mice

“…The viability of the eggs may influence the pathogenesis in the UB but it is unknown. One study described viable and dead eggs were mixed in the intestinal tissue of S. mansoni infected mice [21]. The mice were kept for 69 days after the infection and about 1/4 of eggs were found dead in the tissue.…”

CD18 Regulates Monocyte Hematopoiesis and Promotes Resistance to Experimental Schistosomiasis

“…The worms were washed and counted using a dissecting microscope. Intestinal egg viability was measured in fragments of the intestine (terminal ileum), as previously described ( 24 ). The fragments were examined with an optical microscope (100 ×), and 200 eggs/mouse were counted and classified according to the developmental stage as follows: (i) viable immature eggs (1st to 4th stage), (ii) viable mature eggs or (iii) dead eggs.…”

Immunotherapeutic Activities of a DNA Plasmid Carrying the Mycobacterial hsp65 Gene (DNAhsp65)

“…Another interesting data obtained by these investigations is that this immunotherapy might be a valuable tool to shorten the duration of antibacterial treatment (20,39) in addition to enhancing the response against latent TB and MDR-TB (39,40). The results also suggest that DNAhsp65 is able to prevent TB reactivation in immunosuppressed animals (39,40) and could be administered in helminth coinfection cases (42)(43)(44).…”

“…In TB, the results obtained with the DNAhsp65 vaccine containing the gene that expresses the mycobacterial heat shock protein hsp65 showed that this plasmid DNA construction is a product of radical innovation because it acts in all essential and possible points for the control of disease; acts in prevention (29)(30)(31)(32)(33)(34)(35)(36); can be used as a BCG vaccine boost (38,67,70); acts in the immunotherapy of chronic TB (38), MDR-TB (39-41), and TBL (39)(40)(41); can be used concomitantly with antimycobacterial drugs to enhance the therapeutic and immunotherapeutic action (20,39); prevents the reactivation of the infection (39,40); and can act on those individuals with compromised immune systems, as in helminth infections (42)(43)(44).…”

“…Therefore, the DNAhsp65 vaccine seems to efficiently target fibrotic process that arises from pathological infections due to its ability to reduce the Th2 immune response and preserve the lung parenchyma by inhibiting collagen deposition (42). Similarly, simultaneous vaccination with DNASm14 and DNAHsp65 caused an increase in TCD8 + cell numbers and reduced collagen deposition in the hepatic granuloma, demonstrating protection and antifibrotic effects of this combined vaccine strategy (44).…”