[iBET – ITQB Seminar] Vectors carrying heterologous RNA for designing new viral vaccines

ITQB-IBET Seminar

Title: Vectors carrying heterologous RNA for designing new viral vaccines.

Speaker: Carlos Augusto Pereira

Affiliation: Laboratório de Imunologia Viral, Instituto Butantan, Av. Vital Brasil 1500, 05503-900 São Paulo, Brasil

Short CV

Abstract:

Viral vaccines remain the main tool for preventing virus infections. Inactivated viral particles are well known and have had a great impact in viral disease prevention. Nucleic acid vaccines have a good perspective. Attenuated viral vaccines are indeed the best immunogenic vaccines but safety restrictions for their used have been raised. Virus like particle (VLP) vaccines are already in use mimicking the inactivated viral vaccines. Developments for future viral vaccine should comply with more strict requirements for successful induction of protective immunity. Attempts of constructing VLPs containing mRNA or DNA coding for viral proteins have theoretically a good perspective for successful immune response induction. This approach would combine technological achievements obtained with gene therapy vectors with VLP in view of constructing a VLP carrying a nucleic acid coding for non-structural viral proteins (“VLP/RNA” or “VLP/DNA” vaccine). This complex antigen would contain only molecules of the target virus and enable the immunization against structural (S) and non-structural (NS) viral proteins as well as eliciting humoral and cellular immune responses. They would then mimic attenuated viral vaccines characteristics, with the advantages of being prepared in a controlled bioprocess and constituting a chemically defined antigen. Nevertheless several constraints have to be faced in view of developing such a VLP/nucleic acid. On the biological side, we still don’t know quite in detail steps involving nucleic acid encapsidation. On the bioprocess side we have mainly two challenges, one being a VLP/nucleic acid quantification which has to be based both on protein and nucleic acid methods, and the other being related to the instability of nucleic acids. Manufacturing, formulation and storage have to be developed according to these VLP/nucleic acid characteristics. We will present the rational for developing VLP/nucleic acid vaccines, evidences of their overall protective immune response generation as well as a methodology for VLP/nucleic
acid titration by qPCR and an up to date cell culture bioprocess approach on disposable bioreactors.