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Safety concern of recombination between self-amplifying mRNA vaccines and viruses is mitigated in vivo

Tessy A H Hick1, Corinne Geertsema1, Wilson Nguyen2

  • 1Laboratory of Virology, Wageningen University and Research, Wageningen, the Netherlands.

Molecular Therapy : the Journal of the American Society of Gene Therapy
|June 19, 2024
PubMed

Insights

Self-amplifying mRNA (SAM) vaccines are rapidly deployable, but recombination with other viruses is a safety concern. Studies show recombination is rare in vivo, significantly mitigating risks associated with SAM vaccine use.

Area of Science:

  • Virology
  • Vaccinology
  • Molecular Biology

Background:

  • Self-amplifying mRNA (SAM) vaccines offer rapid deployment during outbreaks.
  • A key safety consideration is potential recombination between alphavirus-based SAM vaccines and co-infecting viruses.

Purpose of the Study:

  • To assess the risk of RNA recombination between SAM vaccines and various alphaviruses and a coronavirus.
  • To evaluate the in vitro and in vivo emergence and fitness of potential chimeric viruses.

Main Methods:

  • Extensive in vitro and in vivo studies involving SAM vaccines, diverse alphaviruses, and a coronavirus.
  • Sensitive cell-based assays and animal models (C57BL/6J, Rag1-/- , Ifnar-/- mice) were utilized.
  • Co-infection and co-replication dynamics were analyzed.

Main Results:

  • SAM vaccines demonstrated superinfection exclusion against alphaviruses, though some co-replication occurred.
  • Replication-competent alphavirus chimeras were generated in vitro via rare recombination events, but showed no increased fitness.
  • No viable alphavirus chimeras were detected in vivo, even under conditions of high co-replication.
  • No recombination was observed between a SAM-spike vaccine and a swine coronavirus.

Conclusions:

  • While RNA recombination between SAM vaccines and alphaviruses is theoretically possible, it is a rare event.
  • In vivo emergence of chimeric viruses is substantially mitigated by multiple factors, including superinfection exclusion and lack of chimera fitness.
  • The environmental safety concern regarding SAM vaccine recombination is significantly reduced based on these findings.
Keywords:
RNA recombinationSAM vaccinealphaviruschimeracoronavirusrepliconsafety concernself-amplifying mRNAsuperinfection exclusion

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