Dendritic cell targeting with a DNA vaccine encoding the domain iii of the protein e of dengue virus

Abstract

Dengue fever is an infection caused by the Dengue virus (DENV), infecting millions of people every year, causing symptoms such as fever, diarrhea, headaches and vomit. Despite its epidemiological importance and increasing incidence, an effective vaccine against DENV is still to be developed. One of the antigens used in current dengue vaccines is the viral envelope protein (E). This protein contains 3 domains (EDI, EDII and EDIII). Many studies showed that EDIII has great immunogenic potential because it contains epitopes that induce neutralizing antibodies. DNA vaccines are among vaccination strategies available nowadays. This type of vaccine uses a plasmid encoding the desired antigen sequence. Once the plasmid enters the organism, it can transfect antigen presenting cells (APCs) or other adjacent cells. After the synthesis of the gene of interest, the product is then presented via MHC class I and II on the surface of the plasma membrane, initiating the immune response. The main disadvantage of this kind of vaccination is its relative low immunogenicity. One way to overcome this problem is to use a strategy that aims at targeting the gene product to dendritic cells. Dendritic cells (DCs) are the main APCs of the immune system. Studies involving antigen targeting to DCs have shown an improvement in the induced immune response. Antigen targeting is accomplished by fusing the antigen to a monoclonal antibody that binds to the surface receptor DEC205, expressed by a specific DC subpopulation. In the case of DNA vaccines, it has been demonstrated that immunization of animals with plasmids encoding a chimeric gene containing the variable portion of the light and heavy chains (single-chain variable fragment, scFv) of the monoclonal antibody ±DEC205 fused with the antigen are able to target DCs, improving the immune response in some cases. In this project we have interest in developing a DNA vaccine containing the DENV E protein-derived EDIII fused with a scFv ±DEC205.