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

• Grant number: 17/09902-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2017
• End date: April 30, 2021
• 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

Chikungunya (CHIKV) and Zika (ZIKV) virus infections constitute a public health problem worldwide and to date, no prophylactic vaccine are available. In addition, the fact that there are no specific treatment for these infections and the fact that they are transmitted by the same vector hamper their control. Particularly in ZIKV infection, there are some recent evidence of the association between infection in pregnant women and microcephaly and/or other neurological and ocular changes in fetus. 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. The ability of Dendritic Cells (DCs) to modulate the adaptive immune responses has also been the focus for vaccine development. Previous studies has demonstrated the possibility to target proteins directly to DCs using endocytic receptors expressed on the surface of these cells, such as DEC205 and DCIR2. The use of chimeric DEC205 or DCIR2 monoclonal antibodies (mAbs) coupled to the antigen of interest leads to better antigen presentation. In this context, the main goal of this project is to produce chimeric DEC205 and DCIR2 mAbs fused to CHIKV and ZIKV E protein and their respective EDI/II and EDIII domains. Moreover, we will if this vaccine strategy is able to induce specific humoral and cellular immune response in vivo. (AU)