No Evidence of Pathological Autoimmunity following Mycobacterium Leprae Heat-Shock Protein 65-Dna Vaccination in Mice

Abstract

Heat-shock proteins (HSPs) are currently one of the most promising targets for the development of immunotherapy against tumours and autoimmune disorders. This protein family has the capacity to activate or modulate the function of different immune system cells. They induce the activation of monocytes, macrophages and dendritic cells, and contribute to cross-priming, an important mechanism of presentation of exogenous antigen in the context of MHe class I molecules. These various immunological properties of HSP have encouraged their use in several clinical trials. Nevertheless, an important issue regarding these proteins is whether the high homology among HSPs across different species may trigger the breakdown of immune tolerance and induce autoimmune diseases. We have developed a DNA vaccine codifying the Mycobacterium /eprae Hsp65 (DNAhsp65), which showed to be highly immunogenic and protective against experimental tuberculosis. Here, we address the question of Whether DNAhsp65 immunization could induce pathological autoimmunity in mice. Our results show that DNAhsp65 vaccination induced antibodies that can recognize the human Hsp60 but did not induce harmful effects in 16 different organs analysed by histopathology up to 210 days after vaccination. We also showed that anti-DNA antibodies were not elicited after DNA vaccination. The results are important for the development of both HSP and DNA-based immunomodulatory agents. 1721-727X (2009) Copyright© by DlOLlFE.8.8.s. This publicationand/or article is for individualuse only and may not be further reproducedwithout written permissionfrom the copyrightholder. Unauthorizedreproductionmay result in financial and other penalties 77The dual roles ofheat-shock proteins (HSPs) in the (I). Due to their potential use as immunomodulators in immune system are still a matter of scientific debate a variety of pathological processes, special attention

Recombinant DNA immunotherapy ameliorate established airway allergy in a IL‐10 dependent pathway

“…Our results with mycobacterial Hsp administered as recombinant DNA indicate that the modulation of allergy can be achieved with reduced amounts of DNA. Despite the classical concerns about recombinant DNA in humans, our results and the results of other studies indicate that this type of formulation is safe for humans, does not integrate in the genomic DNA and does not induce autoimmune manifestations [37,38]. In addition, we showed that the suppressive effect conferred by DNA could be enhanced by an additional injection of r-Hsp65 protein into the airway.…”

Microarray Analysis of NF-κB Signaling Pathways in PBMC of Mice Infected by Trichinella Spiralis

“…As the infection progresses, the inflammatory response becomes mast-cell-and T cell-dependent. Moreover, in T. spiralis infection a wide range of inflammatory cytokines such as IL-I, IL-4, IL-6, IL-8, IFN-y and TNF-a and chemokines are produced (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13).…”

Examination of Periodontal Pathogens in Stenotic Valve Specimens and in Whole Blood Samples in Patients Affected by Aortic Valve Stenosis and Chronic Periodontitis

“…Nakano and colI. (3) analyzed extirpated heart valves to detect cariogenic Streptococcus mutans, the only study in which aortic valves were analyzed to detect oral microorganisms (4)(5). However, the only bacteria which was detected in the analysis of the extirpated heart valves was S. Mutans.…”