mRNA vaccines (BNT162b2 / mRNA-1273) for SARS-CoV-2 utilize lipid nanoparticles (LNPs) for delivery. The mRNA encodes the spike protein. An essential modification in these mRNA vaccines that increases stability and reduces innate immune activation is:

• A Replacing the 5' cap with internal ribosome entry sites (IRES) from poliovirus
• B Incorporating 5-methylcytidine instead of cytidine to prevent RNase-mediated degradation
• C Substitution of uridine with N1-methylpseudouridine (m1Ψ) throughout the mRNA sequence ✓
• D Using circular RNA (circRNA) topology to prevent exonuclease degradation

Explanation

A critical innovation enabling mRNA vaccine technology (developed by Katalin Karikó and Drew Weissman, Nobel Prize 2023) is the substitution of uridine with N1-methylpseudouridine (m1Ψ). Unmodified mRNA contains uridine, which is recognized by innate immune pattern recognition receptors (TLR3, TLR7, TLR8, RIG-I) as non-self, triggering interferon responses that degrade the mRNA and cause adverse effects. m1Ψ substitution evades TLR7/8 detection, dramatically reduces innate immune activation, increases translational efficiency (mRNA is better translated by ribosomes), and improves mRNA stability. This modification made clinical mRNA vaccines feasible. Both Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) use this modification.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.