Development of an effective and safe anti-Zika Virus vaccine using chimeric VLPs expressing Envelope Domain III (E-DIII) protein

• Grant number: 21/03508-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: May 01, 2021
• Status: Discontinued
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Gustavo Cabral de Miranda
• Grantee: Nelson Côrtes de Oliveira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 19/14526-0 - Development of vaccines against Streptococcus pyogenes and Chikungunya Virus based on virus like particles, AP.JP
• Associated scholarship(s): 24/08185-4 - Development of an mRNA Vaccine Against Zika virus Targeting the Domain III of the Envelope Protein, BE.EP.DD

Abstract

The Zika Virus (ZIKV) is a flavivirus transmitted by the bite of arthropods of the genus Aedes, but also through blood transfusion, through sexual or maternal-fetal routes. Since its discovery in 1947, its infection was previously restricted to mild and subclinical cases, however, a major outbreak that began in 2015 in Brazil, has called the attention of public health authorities, since the infection of this pathogen is related to diseases such as Microcephaly and Guillain-Barré Syndrome. ZIKV is able to adhere to neuroprogenitor cells and trigger apoptosis in them, resulting in congenital Zika syndrome. As a result, the development of prophylactic methods has become a global objective. However, in order to formulate an effective vaccine, an epitope must be found that prevents the formation of a cross-reaction of neutralizing antibodies and does not trigger an increase in Antibody-Dependent Infection (ADE). For this reason, Domain III of the viral envelope has been shown to be the best target, since the antibodies that recognize this domain are broadly specific for each flavivirus and/or serotype. In addition, it is necessary to use components with adjuvant characteristics, thus emerging the possibility of developing new effective and safe platforms such as VLPs, which are virus-like particles, to stimulate the immune response and enhance the immune action against the desired antigen. Within this context, our study aims to develop an effective and safe chimeric vaccine against ZIKV, based on VP1VLPs containing the virus E-III protein. (AU)