Therapeutic DNA Vaccine Reduces Schistosoma mansoni–Induced Tissue Damage through Cytokine Balance and Decreased Migration of Myofibroblasts

Abstract

Helminths are known to elicit a wide range of immunomodulation characterized by dominant Th2-type immune responses. Our group previously showed that a DNA vaccine encoding the mycobacterial 65-kDa heat shock protein (DNA-hsp65) showed immunomodulatory properties. We also showed, using a helminth-tuberculosis (TB) co-infection model, that the DNA-hsp65 vaccine protected mice against TB. We next investigated the mechanistic role of the vaccine during helminth-TB co-infection. Clinically, helminth infection causes type 2 granulomas in the lung. Mice were immunized with DNA-hsp65 while they were submitted to the type 2 granuloma induction protocol by Schistosoma mansoni eggs infusion. In this work we investigated the effects of DNA-hsp65 on the pathology and immune response during the development of type 2 granuloma induced by S. mansoni eggs. Histologic analyses of lung parenchyma showed that the DNA-hsp65 vaccine protected mice against exacerbated fibrosis induced by Schistosoma eggs, and decreased the size of the granulomas. These changes were correlated with a reduction in the number of T cells specific for the egg antigens in the lung and also with modulation of Th2 cytokine expression. Taken Helminth infections are widespread in the tropics, and are known to elicit a wide range of immunomodulation effects characterized by dominant T helper cell (Th) 2-type immune responses, chronic immune activation, as well as up-regulated regulatory T-cell activity. Our group previously showed that a DNA vaccine encoding the mycobacterial 65-kDa heat shock protein (DNA-hsp65), that protected mice and guinea pigs against tuberculosis (TB), 1-3 also showed immunomodulatory properties in other diseases. 4 -7 We also showed that this DNA-hsp65 vaccine protected mice against TB in a helminth-TB co-infection model. 8 These results led us to investigate the mechanistic role of the vaccine during helminth-TB co-infection.One of the clinical manifestations of helminth infection is the presence of type 2 granulomas. The lung is the primary site of organ involvement in a range of granulomatous conditions. 9 The immune response to Schistosoma mansoni eggs in mice results in the development of hepatic, intestinal, and pulmonary granulomas that lead to extensive fibrosis. 10,11 The cellular composition of the granulomas includes eosinophils, alternatively activated (M2) macrophages, lymphocytes, neutrophils, mast cells, and fibroblasts. 12 Further, the recruitment and migration of these cells into the site of inflammation are controlled by cytokines and chemokines. The complex cytokinechemokine regulatory network has been well established, and dictates the profile of local chemokine expression during T-cell-mediated type 2 lung granuloma formation as a result of S. mansoni egg injection. 13,14 To induce granulomas we used a system based on the embolization of S. mansoni eggs to the lungs. This approach leads the release of glycoproteins, referred to as S. mansoni soluble egg antigen (SEA), inducing a strong polarization of

Recombinant Lactobacillus casei Expressing Capsid Protein VP60 can Serve as Vaccine Against Rabbit Hemorrhagic Disease Virus in Rabbits

“…Previous studies have shown that capsid protein VP60(VP1), a major immunogenic protein of RHDV, induces expression of a neutralizing antibody [41]. Rabbits inoculated with a sufficient amount of recombinant VP60(VP1) are fully protected from wild-type RHDV, and VP60 is commonly used to develop recombinant engineered vaccines against RHDV [41,42]. Therefore, VP60(VP1) was selected as an immunogen for the development of a recombinant engineered vaccine in this study.…”

Immunotherapeutic efficacy of recombinantMycobacterium smegmatisexpressing Ag85B–ESAT6 fusion protein against persistent tuberculosis infection in mice

“…25,26 Recent therapeutic development has brought into focus an attractive strategy by screening and validating specific target antigens to boost the existed Th1-type immune responses in persistent Mtb-infected individuals, which minimizes pathological damages induced by granuloma formation and tissue inflammation. 27,28 Both Ag85B and ESAT6 can induce strong immune responses in animal models of tuberculosis. 29 ESAT6 is a dominant inducer of immune responses during primary or latent infection, and this antigen shows strong association with latent infection.…”

Soil-Transmitted Helminth Vaccines: Are We Getting Closer?

“…For example, the human immunodeficiency virus-1 (both as a prophylactic and an immunotherapeutic vaccine) ( 58 , 59 ), Zika virus ( 60 ), and Ebola virus vaccines ( 61 ) are currently in clinical trials. Comparatively, little progress has been made toward developing DNA vaccines against parasitic diseases, although several pre-clinical studies have shown promising results against hookworm infections ( 62 , 63 ), malaria ( 64 , 65 ), leishmaniasis ( 66 , 67 ), and schistosomiasis ( 68 , 69 ). Even though DNA vaccines offer several advantages when compared with recombinant vaccines, such as safety, improper protein folding and production cost, they have not been shown to be sufficient to induce a protective immune response ( 70 ).…”