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#mRNA vaccines

2 public questions tagged with this topic.

Which of the following is an mRNA vaccine?

Pfizer-BioNTech BNT162b2 Comirnaty exemplifies messenger RNA vaccine success. It contains 30 microgram dose of nucleoside modified mRNA encoding full length SARS-CoV-2 spike protein stabilized in prefusion conformation by double proline substitution K986P V987P preventing post fusion transition, retaining epitopes for neutralizing antibodies. mRNA produced by cell free transcription, purified to remove dsRNA impurities that trigger innate over activation. LNP formulation enables efficient transfection without electroporation. After emergency use authorization December 2020, phase three trial i

Ref: Polack et al. NEJM 2020 383:2603 Pfizer-BioNTech mRNA; CDC mRNA vaccines list; FDA Comirnaty.

mRNA vaccines work by:

Messenger RNA vaccines represent nucleic acid platform delivering synthetic mRNA encoding pathogen antigen directly to host cytoplasm where host ribosomal machinery translates it transiently. Manufacturing involves in vitro transcription using T7 RNA polymerase from linearized plasmid DNA template encoding spike protein, incorporation of modified nucleoside N1 methylpseudouridine replacing uridine reducing TLR7 mediated inflammation and increasing translation half-life, addition of 5' cap 7-methylguanosine via vaccinia capping enzyme and 2'O-methylation, and 3' polyadenine tail 100 nt for stab

Ref: Pardi et al. Nat Rev Drug Discov 2018 mRNA mechanism; Polack NEJM mRNA; CDC mRNA work.