Characterization of BNT162b2 mRNA to Evaluate Risk of Off-Target Antigen Translation

mRNA vaccines have been established as a safe and effective modality, thanks in large part to the expedited development and approval of COVID-19 vaccines. In addition to the active, full-length mRNA transcript, mRNA fragment species can be present as a byproduct of the cell-free transcription manufa...

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Bibliographic Details
Published in:	Journal of pharmaceutical sciences Vol. 112; no. 5; p. 1364
Main Authors:	Patel, Himakshi K, Zhang, Kun, Utegg, Rachael, Stephens, Elaine, Salem, Shauna, Welch, Heidi, Grobe, Svenja, Schlereth, Julia, Kuhn, Andreas N, Ryczek, Jeff, Cirelli, David J, Lerch, Thomas F
Format:	Journal Article
Language:	English
Published:	United States 01-05-2023
Subjects:	Antibodies, Viral BNT162 Vaccine COVID-19 COVID-19 Vaccines Humans RNA, Messenger - genetics SARS-CoV-2 - genetics COVID-19 Vaccine mRNA Comirnaty HPLC
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Summary:	mRNA vaccines have been established as a safe and effective modality, thanks in large part to the expedited development and approval of COVID-19 vaccines. In addition to the active, full-length mRNA transcript, mRNA fragment species can be present as a byproduct of the cell-free transcription manufacturing process or due to mRNA hydrolysis. In the current study, mRNA fragment species from BNT162b2 mRNA were isolated and characterized. The translational viability of intact and fragmented mRNA species was further explored using orthogonal expression systems to understand the risk of truncated spike protein or off-target antigen translation. The study demonstrates that mRNA fragments are primarily derived from premature transcriptional termination during manufacturing, and only full-length mRNA transcripts are viable for expression of the SARS-CoV-2 spike protein antigen.
ISSN:	1520-6017
DOI:	10.1016/j.xphs.2023.01.007