Replicons ready to recombine? Assessing chimerization between self-amplifying mRNA vaccines and wild-type viruses

Summary

mRNA vaccines became a leading technology to combat emerging infectious diseases during the SARS-CoV-2 pandemic. Currently, a next generation of self-amplifying mRNA (replicon) vaccines is on the rise. These replicons use an alphavirus replicase for self-amplification and consequently induce a potent immune response at a lower vaccine dose. A theoretical safety concern has been raised concerning the possibility of interactions, in the form of RNA recombination, between the alphavirus-based replicon vaccine and wild-type viruses circulating in nature. Such a recombination event might result in chimeric viruses with unpredictable phenotypes. To experimentally evaluate this safety concern, we studied the ability of an alphavirus-based replicon vaccine to recombine with wild-type viruses in cell cultures and animal models.

Overall, these experiments illustrated a low potential for RNA recombination between an alphavirus-based replicon vaccine and circulating viruses in vaccinated individuals.