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https://www.cell.com/molecular-therapy-family/molecular-therapy/pdf/S1525-0016(24)00401-5.pdf

Original Article
Safety concern of recombination
between self-amplifying mRNA vaccines
and viruses is mitigated in vivo
åèè«æ èªå·±å¢å¹ mRNAã¯ã¯ãã³ãšãŠã€ã«ã¹éã®çµã¿æãã®å®å šæ§ã®æžå¿µã¯çäœå ã§è»œæžããã
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-replica-
tion was still possible. Using sensitive cell-based assays, replica-
tion-competent alphavirus chimeras were generated in vitro as
a result of rare, but reproducible, RNA recombination events.
The chimeras displayed no increased ï¬tness in cell culture.
Viable alphavirus chimeras were not detected in vivo in
C57BL/6J, Rag1Ã/Ã and IfnarÃ/Ã 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 recip-
ients.
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1) Alden M et al., Intracellular reverse transcription of Pfizer BinNTech COVID-19 mRNA vaccine BNT162b2 in vitro in human liver cell line. Curr Issues Mol Biol, Feb 25, 2022.
2) Hick TAH, et al., Safety concern of recombination between self-amplifying mRNA vaccines and viruses is mitigated in vitro. Mol Ther, Aug, 2024.
(2024.9.30)
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