Nanovaccines: a novel experimental concept applied to the development of subunit vacines.

Abstract

Over the last years viruses from Flavivirus family have been responsible for several epidemies, gaining special notoriety in Brazil for the resurgence of Yellow Fever and Zika virus (ZIKV) association with neurological syndromes. WHO regards the development of safe and efficient vaccines against these pathogens a priority. In this context subunit vaccines are particularly promising for being safer, despite being associated with lower immunogenicity. In the present project we propose a novel experimental approach applied to the development of subunit vaccines, consisting in the modification of recombinant proteins through the insertion of cationic peptides that confer to the antigen self assembling properties ("Self Assembling Protein Nanoparticles"). We propose to apply the concept of nanovaccines to the envelope protein (E), and in particular to the domain III (EDIII) of flavivirus, initially with emphasis on ZIKV. Additionally, cationic peptides can confer enhanced internalization capacity, thus mimicking both size and behavior characteristics of viral particles. We expect the nanovaccines prepared with EDIII and other parts of E protein from flavivirus to increase immunogenicity and stability of target antigens, achieving the induction of durable and broader immune responses, including T-cell mediated immunity. As a final goal, we seek the implementation of a novel vaccine strategy so far unexplored in Brazil, that could be applied to other flavivirus and viruses in general.