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 alphavi...
| Authors | Hick, TAH; Geertsema, C; Nguyen, W; van Oosten, L; Bishop, CR; Abbo, SR; Dumenil, T; van Kuppeveld, FJM; Langereis, MA; Rawle, DJ; Tang, B; Yan, K; van Oers, MM; Suhrbier, A; Pijlman, GP |
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| Journal | Molecular therapy : the journal of the American Society of Gene Therapy |
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| Date | 17/07/2024 |
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| URL | http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1016/j.ymthe.2024.06.019 |