Targeting dendritic cells in vivo with recombinant gp43: a new strategy for vaccine development in paracoccidioidomycosis

Abstract

The paracoccidioidomycosis (PCM) is a granulomatous mycosis of nature, which jeopardizes preferably lung tissue, the lymphatic system, the mucocutaneous tissue and, by extension, any other organ. It is caused by a thermally dimorphic fungus, Paracoccidioides brasiliensis, whose main component is a antigêncico 43 kDa glycoprotein (gp43). The gp43 is immunoreactive for 100% of sera from patients infected and not react with sera from control individuals.Dendritic cells (DCs) are critical in the process of induction of immunity and peripheral tolerance (Banchereau, Steinman, 1998; Steinman et al. 2000). This fact opens up the possibility that these cells may be targets of possible manipulations aimed at inducing or generating immunotherapeutic suppressor of immune response. Recently, it was shown that you can send directly to the CD antigens (HAWIGER et al., 2001; BONIFAZ et al., 2002). When this occurs in the absence of concomitant inflammatory stimulus, the result is the induction of immunological tolerance (HAWIGER et al. 2001; HAWIGER et al. 2004). Furthermore, when the antigen is sent to these same cells in the presence of an inflammatory stimulus, the result is the induction of a strong immune response (BONIFAZ et al. 2004; Boscardin et al. 2,006; TRUMPFHELLER et al. 2006). The targeting of the antigen to the DCs in vivo is accomplished by administering low doses of a recombinant protein consisting of a chimeric monoclonal antibody specific for receptors present on the surface of CDs in fusion with the antigen of interest. The monoclonal antibody having the capacity to bind to the DEC 205 receptor (anti-DEC 205, Inaba et al. 1995; SWIGGARD et al. 1995; Witmer-Pack et al. 1995), showed that are potent immunogens capable of inducing cellular immunity (T lymphocyte-mediated CD4 + and CD8 +) and lasting humoral against the antigen of interest (Boscardin et al. 2,006; TRUMPFHELLER et al. 2006).Thus, the main objective of this project is to use anti-chimeric antibodies 33D1 or DEC 205 in fusion with gp43 in immunization protocols in order to obtain effective immunogens that can be used for prevention or for the treatment of PCM. (AU)