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#mRNA vaccines

2 public questions tagged with this topic.

Vaccine

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 in 43,000 participants demonstrated 95 percent efficacy against symptomatic COVID-19 confirmed by RT-PCR and 100 percent against severe disease initially. Unlike Covaxin whole virion inactivated requiring BSL-3 production, Covishield chimpanzee adenovirus vector, BCG live mycobacterial tuberculosis vaccine unrelated to COVID, Comirnaty mRNA platform demonstrates synthetic biology rapid response with manufacturing cycle weeks versus months. Cold chain ultralow freezer minus 80C required initially due to RNA lability but later stability data supported minus 20C and 2-8C thawed short term. Subsequent bivalent versions encoding Omicron BA.4-5 spike illustrate adaptability updating coding sequence while keeping LNP chemistry identical for future pandemics.

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

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Vaccine

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 stability. mRNA encapsulated in lipid nanoparticles LNP composed of ionizable lipid ALC-0315 or SM-102 protonated at low pH encapsulating RNA, helper lipid DSPC forming bilayer, cholesterol fluidity, and PEGylated lipid reducing aggregation and prolonging circulation. Upon intramuscular injection LNPs fuse with cell membrane or endocytosed, ionizable lipid becomes cationic at endosomal low pH disrupting endosome releasing mRNA to cytosol. Ribosomes translate antigen protein undergoing post translational modifications, secreted or membrane anchored, processed for MHC I and II presentation inducing neutralizing IgG and CD4 Th1 and CD8 cytotoxic memory. mRNA degraded within days by RNases no integration risk enabling rapid design.

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

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