Targeting antigens to dendritic cells in vivo: a new strategy for vaccine development in Paracoccidioidomycosis

Author(s)

Suelen Silvana dos Santos

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2014-11-27

Examining board members

Sandro Rogerio de Almeida; Wagner Luiz Batista; Daniela Santoro Rosa

• Advisor: Sandro Rogerio de Almeida

Abstract

Paracoccidioidomycosis (PCM) is the most common systemic mycosis in Brazil. In the last decade, it was demonstrated that antigens can be directly target to the dendritic cells using the antibody αDEC205 in the presence of a maturation stimulus, resulting in the induction of a strong immune response. We found that αDEC205 antibody fused to peptide P10 induced great response by IFN-γ producing cells after a single dose in relation to the administration of P10, although it has been administered in a lower concentration. However, this response was not maintained after second dose of antibody. Animals challenge with P. brasiliensis, after immunization with two doses of the chimeric antibody, produced high levels IFN-γ and IL-4 in lung tissue significantly higher in αDEC/P10 group in relation to the administration of P10, all in the presence of Poly I:C. In therapy assays, we found in the lungs of mice treated with the chimeric antibody, the main organ involved in an animal model of PCM, low concentration of IFN-γ and IL-10 compared to controls. In addition, it became evident that animals treated with αDEC/P10 antibody have a lung tissue much closer to that of non-infected tissue, while in the absence of suitable treatment we find clusters of yeasts and tissue filled with cellular infiltrates. Altogether, these findings show a clinical improvement in treated animals and indicate that targeting of P10 through the chimeric antibody αDEC/P10 in the presence of Poly I:C, is a promising strategy for therapy against P. brasiliensis. (AU)

• FAPESP's process: 10/50439-0 - Targeting dendritic cells in vivo with recombinant gp43: a new strategy for vaccine development in paracoccidioidomycosis
• Grantee: Suelen Silvana dos Santos
• Support Opportunities: Scholarships in Brazil - Doctorate