RNA recombination between self-amplifying RNA vaccines and wild-type viruses

Abstract

Self-amplifying RNA vaccines based on alphavirus replicon vectors are considered the next-generation of mRNA vaccines as they induce protective immune responses upon single low-dose administration. The replicative character of these replicon vaccines provides high level expression of the antigen of interest, e.g. a coronavirus spike protein. However, the replicative character of this novel vaccine platform also creates the hypothetical risk of RNA recombination between the self-replicating alphavirus replicon and circulating wild-type viruses. To experimentally address this possibility, co-infections were conducted of alphavirus replicons and wild-type alphaviruses, as well as alphavirus replicons expressing a coronavirus spike gene and a wild-type coronavirus. In few occasions, and only with specific co-infection conditions and combinations, chimeras were detected in vitro. Current work is ongoing to quantify the incidence of RNA recombination in vivo to provide further input for the environmental safety assessment of the alphavirus replicon vaccine platform.

Biography

Tessy Hick is a PhD student in the arbovirology group of Dr. Gorben Pijlman at Wageningen University, the Netherlands. She is driven by curiosity to study fundamental virology questions with an applied perspective to improve global health. She previously developed a baculovirus-expressed chikungunya virus vaccine (MSc thesis, Laboratory of Virology, Wageningen University), and studied the large scale application of this baculovirus expression system in suspension insect cells (MSc thesis, Bioprocess Engineering department, Wageningen University). Furthermore, she developed a scalable production process for adeno-associated virus gene therapy vectors by transient transfection of HEK293 suspension cells (MSc internship, Translational Vectorology Group, Children’s Medical Research Institute, Sydney, Australia). Currently, Tessy assesses the environmental safety of alphavirus-based, self-replicating RNA vaccines (replicons), focusing on the potential risk of RNA recombination between replicon vaccines and circulating viruses. To study this process in vivo, she collaborates with the group of Prof. Andreas Suhrbier at the Queensland Institute of Medical Research Berghofer in Brisbane, Australia.