B and T cell responses elicited by monoclonal anti-idiotypic antibody (Ab2β) mimicking gp43 fromParacoccidioides brasiliensis

Abstract

SUMMARYParacoccidioidomycosis is a systemic mycosis endemic in Latin America, with a high prevalence in Brazil, Argentina, Colombia and Venezuela. The aetiological agent of disease is the thermal dimorphic fungus, Paracoccidioides brasiliensis . A glycoprotein of 43 kD (gp43) is the major antigen of P. brasiliensis . Antibodies directed to this antigen are detected in the sera of all patients with paracoccidioidomycosis (PCM). Recently, it has been shown that mice immunized with anti-gp43 monoclonal antibodies (MAbs) (Ab1), induce the idiotypic cascade in the gp43 system, which produced both, anti-Id antibodies (Ab2) and anti-anti-Id antibodies (Ab3). To further characterize the idiotypic cascade modulation in mice immunized with anti-gp43 MAb 17c, hybridomas were produced. Ab2 MAbs named 7.B12 inhibited ( > 95%) the binding of gp43 to MAb 17c (Ab1), suggesting that this anti-Id MAb bind to the idiotope, thus fulfilling the internal image criteria. To elucidate whether Ab2 MAb could act as antigen in serological assays, instead of gp43, sera from PCM patients were tested. Using an ELISA test, it was observed that antibodies from patients and not normal serum bound to Ab2. However, the ELISA test using Ab2 bound to the solid phase made possible to serologically monitor the patients after antifungal therapy, showing an equivalent curve when compared with ELISA test employing purified gp43. Our results also showed that, when mice were immunized with Ab2 b and their cells were exposed to gp43 in vitro , a T cell proliferation response was observed.

Paracoccidioides brasiliensis Vaccine Formulations Based on the gp43-Derived P10 Sequence and the Salmonella enterica FliC Flagellin

“…The extracellular gp43 glycoprotein, the major diagnostic antigen of P. brasiliensis, is the most intensively studied component aimed at a vaccine for PCM control. Previous reports have shown that mice immunized with the purified protein, DNA, or anti-idiotypic monoclonal antibody were partially protected against challenges by P. brasiliensis (28,36,37,40). A 15-amino-acid peptide (QTLIAIHTLAIRY AN), designated P10, contains the gp43 immunodominant CD4 ϩ T-cell-specific epitope presented by major histocompatibility complex class II molecules from three different mouse haplotypes (37) and most human HLA-DR alleles (17, 18).…”

Maintenance of antigen‐specific immunological memory through variable regions of heavy and light chains of anti‐idiotypic antibody

“…Anti‐idiotypic antibodies with homologous sequences to specific regions of the immunogenic proteins of infectious organisms have been shown to functionally mimic these epitopes and to induce protective immune responses; 21,22 they have been used in experimental systems as surrogate vaccines against several bacterial, 23 viral 22,24–27 and parasitic organisms 21,28 and as several tumour‐associated antigens 13,29 . It has been shown that a murine Ab 2 mimicking a peptide of hepatitis B surface antigen expressed epitopes for both B and T cells.…”

scFv from Antibody That Mimics gp43 Modulates the Cellular and Humoral Immune Responses during Experimental Paracoccidioidomycosis

“…In 2004, a T cell proliferative response was demonstrated following the immunization of mice with an Ab2-β Mab (7.B12) and their subsequent exposure to gp43 in vitro , indicating that this molecule contains a T cell epitope [ 7 , 8 ]. However, the use of this antibody can cause damage to the host due to its size and induction of an unspecific immune response.…”

“…brasiliensis modulates the immune response. After P10 plasmid immunization, a stronger protective immune response involving a CD4 + T cell epitope has been observed [ 8 ]. DNA vaccination has shown therapeutic effects in experimental PCM based on a reduction in fungal burden [ 9 – 11 ].…”