Infectious Disease · 2020
BNT162b2 mRNA COVID-19 Vaccine (Pfizer-BioNTech)
BioNTech/Pfizer COVID-19 vaccine, tozinameran (Comirnaty)
On January 10, 2020, a group of Chinese scientists posted the complete genetic sequence of a novel coronavirus to an international database. Within days, Ugur Sahin, the CEO of BioNTech, had identified the spike protein as the target for an mRNA vaccine candidate. That speed was possible because mRNA vaccine design 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 in 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 partnered with BioNTech in April 2020 to co-develop BNT162b2 and provide 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 interim 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, less than eleven months after the viral sequence was published. Operation Warp Speed, the U.S. government program that pre-purchased doses and funded manufacturing scale-up before efficacy data were available, allowed Pfizer and BioNTech to have doses ready for distribution within days of authorization. Albert Bourla, Pfizer's CEO, had committed the company to producing hundreds of millions of doses on that speculative basis. 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 generated immediate and intensive scrutiny of mRNA technology across infectious disease applications, accelerating programs for RSV, influenza, and cancer neoantigen vaccines that had been advancing slowly. The regulatory precedent established for an mRNA vaccine under emergency conditions also influenced how subsequent mRNA products for non-COVID indications navigated agency review.
Key People
- Ugur Sahin — BioNTech CEO and lead vaccine designer
- Katalin Kariko — BioNTech SVP; developed modified mRNA to reduce immunogenicity
- Drew Weissman — Penn immunologist; co-developed modified nucleoside mRNA technology
- Albert Bourla — Pfizer CEO; oversaw manufacturing scale-up and distribution
- Ozlem Tureci — BioNTech CMO and co-founder; oversaw clinical development of BNT162b2
N Engl J Med. 2020;383(27):2603-2615
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