BNT162b2 mRNA COVID-19 Vaccine (Pfizer-BioNTech)

On January 10, 2020, a group of Chinese scientists posted the complete genetic sequence of a novel coronavirus to an international database. Two weeks later, after reading a report in The Lancet describing human-to-human transmission, Ugur Sahin, the CEO of BioNTech, decided to pursue a vaccine and identified the spike protein as its target. That decision could move quickly into design work because mRNA vaccine development does not require growing virus in culture or manufacturing recombinant protein: once you have the genetic sequence of your antigen, you can encode it in mRNA and begin designing lipid nanoparticle delivery within days. BioNTech had been developing its mRNA platform for cancer immunotherapy and had never brought an infectious-disease vaccine to a phase 3 trial.

The foundational technology underlying BNT162b2 owed a great deal to work done years earlier by Katalin Kariko and Drew Weissman at the University of Pennsylvania. Kariko, who spent years at Penn pursuing mRNA therapeutics without major institutional support, and Weissman showed that substituting modified nucleosides for uridine in mRNA dramatically reduced the innate immune response that would otherwise degrade the molecule before it could be translated. That modification made it possible to dose mRNA repeatedly in humans, a prerequisite for a vaccine requiring two doses. BioNTech licensed the technology and Kariko later joined the company as Senior Vice President.

Pfizer agreed to co-develop BNT162b2 with BioNTech in March 2020 and signed a global collaboration agreement in April, providing the manufacturing and distribution infrastructure BioNTech did not have at scale. The phase 3 trial enrolled 43,548 participants across six countries, randomizing them to two doses of the vaccine or placebo given 21 days apart. Participants were followed for symptomatic COVID-19 confirmed by PCR. The primary efficacy analysis, conducted after 170 COVID-19 cases had accrued, showed 95% efficacy: 8 cases in the vaccine group versus 162 in the placebo group.

The FDA issued an Emergency Use Authorization on December 11, 2020, about eleven months after the viral sequence was published. A $1.95 billion advance purchase agreement that Pfizer and BioNTech signed with the U.S. government in July 2020, under the Operation Warp Speed initiative, guaranteed a market for 100 million doses without funding the companies' research or manufacturing; Pfizer financed that scale-up itself. Albert Bourla, Pfizer's CEO, committed the company to manufacturing hundreds of millions of doses at its own financial risk before authorization was granted. First doses were administered in the United States on December 14, 2020.

BNT162b2 was the first mRNA vaccine ever authorized for human use, after decades of platform development that had not previously yielded a licensed product. The authorization brought immediate and intensive scrutiny of mRNA technology across infectious disease applications, and programs for RSV, influenza, and cancer neoantigen vaccines that had been advancing slowly picked up speed. The regulatory precedent set for an mRNA vaccine under emergency conditions also shaped how subsequent mRNA products for non-COVID indications moved through agency review.