Production of anti-DEC205 antibodies fused to Chikungunya and Zika virus proteins for antigen targetting in vivo

• Grant number: 16/03965-5
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): May 01, 2016
• Effective date (End): June 30, 2017
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Daniela Santoro Rosa
• Grantee: Fernanda Caroline Coirada Oliveira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Infections by Chikungunya (CHIKV) and Zika (ZIKV) viruses currently constitute a public health problem worldwide and to date, there are no available prophylactic vaccines. Moreover, the fact that there are no specific medications for these infections and the fact that they are transmitted by the same vector difficult their control. In recent years, various immunogen production platforms have been explored for the purpose of producing a vaccine capable of preventing infection by CHIKV. The main challenge is to find the balance between immunogenicity and safety of the vaccine formulation. Regarding ZIKV, until the moment no candidate antigen was evaluated as an immunogen. The envelope glycoproteins of CHIKV and ZIKV are the most abundant on the surface of virions and are involved in the binding process and fusion with the target cell membrane. Because of these characteristics, they are important targets for antibodies, and may be considered important antigens for use as vaccines. Knowledge of the biology of dendritic cells (DCs) has allowed the development of vaccine strategies based on the ability of these cells to modulate humoral and cellular immune responses. From previous studies, it was found the possibility to target proteins directly to DCs by endocytic receptors expressed on the surface of these cells, as DEC205. The use of chimeric ±-DEC205 monoclonal antibodies (mAbs) coupled to the antigen of interest lead to a better antigen presentation. In this project we intend to generate chimeric ±-DEC205 mAbs fused to CHIKV E1 and E2, and ZIKV E proteins. Subsequently, these vaccine candidates will be evaluated for immunogenicity in mice and specific humoral and cellular immune responses will be evaluated. (AU)