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Safety concern of recombination between self-amplifying mRNA vaccines and viruses is mitigated in vivo.
Hick, Tessy A H; Geertsema, Corinne; Nguyen, Wilson; Bishop, Cameron R; van Oosten, Linda; Abbo, Sandra R; Dumenil, Troy; van Kuppeveld, Frank J M; Langereis, Martijn A; Rawle, Daniel J; Tang, Bing; Yan, Kexin; van Oers, Monique M; Suhrbier, Andreas; Pijlman, Gorben P.
Afiliação
  • Hick TAH; Laboratory of Virology, Wageningen University and Research, Wageningen, the Netherlands.
  • Geertsema C; Laboratory of Virology, Wageningen University and Research, Wageningen, the Netherlands.
  • Nguyen W; Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia.
  • Bishop CR; Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia.
  • van Oosten L; Laboratory of Virology, Wageningen University and Research, Wageningen, the Netherlands.
  • Abbo SR; Laboratory of Virology, Wageningen University and Research, Wageningen, the Netherlands.
  • Dumenil T; Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia.
  • van Kuppeveld FJM; Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, the Netherlands.
  • Langereis MA; Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, the Netherlands.
  • Rawle DJ; Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia.
  • Tang B; Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia.
  • Yan K; Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia.
  • van Oers MM; Laboratory of Virology, Wageningen University and Research, Wageningen, the Netherlands.
  • Suhrbier A; Inflammation Biology Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia; Global Virus Network Centre of Excellence, Australian Infectious Diseases Research Centre, Brisbane, QLD 4072 and 4029, Australia. Electronic address: andreas.suhrbier@qimrberghofer.edu.au.
  • Pijlman GP; Laboratory of Virology, Wageningen University and Research, Wageningen, the Netherlands. Electronic address: gorben.pijlman@wur.nl.
Mol Ther ; 2024 Jun 17.
Article em En | MEDLINE | ID: mdl-38894543
ABSTRACT
Self-amplifying mRNA (SAM) vaccines can be rapidly deployed in the event of disease outbreaks. A legitimate safety concern is the potential for recombination between alphavirus-based SAM vaccines and circulating viruses. This theoretical risk needs to be assessed in the regulatory process for SAM vaccine approval. Herein, we undertake extensive in vitro and in vivo assessments to explore recombination between SAM vaccine and a wide selection of alphaviruses and a coronavirus. SAM vaccines were found to effectively limit alphavirus co-infection through superinfection exclusion, although some co-replication was still possible. Using sensitive cell-based assays, replication-competent alphavirus chimeras were generated in vitro as a result of rare, but reproducible, RNA recombination events. The chimeras displayed no increased fitness in cell culture. Viable alphavirus chimeras were not detected in vivo in C57BL/6J, Rag1-/- and Ifnar-/- mice, in which high levels of SAM vaccine and alphavirus co-replicated in the same tissue. Furthermore, recombination between a SAM-spike vaccine and a swine coronavirus was not observed. In conclusion we state that although the ability of SAM vaccines to recombine with alphaviruses might be viewed as an environmental safety concern, several key factors substantially mitigate against in vivo emergence of chimeric viruses from SAM vaccine recipients.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article