2020: mRNA Vaccines for COVID-19 (2020)

The emergency use authorisations granted by the FDA in December 2020—first to the Pfizer-BioNTech
BNT162b2 mRNA vaccine on 11 December and then to the Moderna mRNA-1273 vaccine on 18 December—
represented the first authorised mRNA vaccines in history and the fastest successful vaccine
development programme ever completed. Both vaccines encode the SARS-CoV-2 spike protein in a
modified mRNA sequence stabilised by two proline substitutions (2P) that lock the spike in its
prefusion conformation, delivered encapsulated in ionisable lipid nanoparticles.

The scientific foundation had been built over more than a decade by Katalin Karikó and Drew
Weissman at the University of Pennsylvania, who discovered in 2005 that substituting
pseudouridine for uridine in mRNA abolished the toll-like receptor-mediated innate immune
response that had made in vitro-transcribed mRNA highly inflammatory and short-lived in vivo.
This modification, combined with advances in LNP formulation pioneered by Pieter Cullis and
colleagues, made stable and immunogenic mRNA delivery feasible. BioNTech and Moderna had
both pursued the platform for cancer neoantigen vaccines and infectious disease applications
prior to the pandemic.

When the SARS-CoV-2 genome sequence was posted on 10 January 2020, both companies—along
with the NIH Vaccine Research Center, which provided the 2P spike stabilisation design—were
able to define vaccine sequences within days and begin manufacturing within weeks. Phase III
trials enrolling 30,000–44,000 participants demonstrated vaccine efficacy of approximately
95 % against symptomatic COVID-19. The unprecedented trial speed was enabled by CEPI funding,
parallel manufacturing during trials, and regulatory rolling review.

Karikó and Weissman were awarded the Nobel Prize in Physiology or Medicine in 2023.