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Safety concern of recombination between self-amplifying mRNA vaccines and viruses is mitigated in vivo
Molecular Therapy ( IF 12.1 ) Pub Date : 2024-06-17 , DOI: 10.1016/j.ymthe.2024.06.019 Tessy A H Hick 1 , Corinne Geertsema 1 , Wilson Nguyen 2 , Cameron R Bishop 2 , Linda van Oosten 1 , Sandra R Abbo 1 , Troy Dumenil 2 , Frank J M van Kuppeveld 3 , Martijn A Langereis 3 , Daniel J Rawle 2 , Bing Tang 2 , Kexin Yan 2 , Monique M van Oers 1 , Andreas Suhrbier 4 , Gorben P Pijlman 1
Molecular Therapy ( IF 12.1 ) Pub Date : 2024-06-17 , DOI: 10.1016/j.ymthe.2024.06.019 Tessy A H Hick 1 , Corinne Geertsema 1 , Wilson Nguyen 2 , Cameron R Bishop 2 , Linda van Oosten 1 , Sandra R Abbo 1 , Troy Dumenil 2 , Frank J M van Kuppeveld 3 , Martijn A Langereis 3 , Daniel J Rawle 2 , Bing Tang 2 , Kexin Yan 2 , Monique M van Oers 1 , Andreas Suhrbier 4 , Gorben P Pijlman 1
Affiliation
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 and 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 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 C57BL/6J, and 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 emergence of chimeric viruses from SAM vaccine recipients.
更新日期：2024-06-17
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