Monoclonal antibody against the major diagnostic antigen of Paracoccidioides brasiliensis mediates immune protection in infected Balb/c mice challenged intratracheally with the fungus

Institute of Biomedical Sciences, Department of Microbiology, University of São Paulo, São Paulo, SP, Brazil; Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, São Paulo, SP, Brazil; Departments of Medicine and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA

^* To whom correspondence should be addressed. Email: taborda{at}usp.br.

	Abstract

The protective role of specific antibodies against Paracoccidioides brasiliensis is controversial. In the present study, we analyzed the effects of monoclonal antibodies to the major diagnostic antigen (gp43) using in vitro and in vivo P. brasiliensis infection models. Passive administration of some mAbs before and after intratracheal or intravenous infections led to reduced fungal burden and decreased pulmonary inflammation. Protection mediated by mAb 3E, the most efficient mAb in the reduction of fungal burden, was associated with enhanced phagocytosis of yeast cells by J774.16, MH-S or primary macrophages. The ingestion of opsonized yeast cells led to an increase in NO production by macrophages. Passive immunization with mAb 3E induced enhanced levels of IFN- in the lungs of infected mice. The reactivity of mAb 3E against a panel of gp43-derived peptides suggested that the sequence NHVRIPIGWAV contains the binding epitope. The present work shows that some but not all mAbs against gp43 can reduce the fungal burden and identifies a new peptide candidate for vaccine development.