Nature . Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults

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Nature


. 2020 Aug 12.
doi: 10.1038/s41586-020-2639-4. Online ahead of print.
Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults


Mark J Mulligan ^{1 2} , Kirsten E Lyke ³ , Nicholas Kitchin ⁴ , Judith Absalon ⁵ , Alejandra Gurtman ⁶ , Stephen Lockhart ⁴ , Kathleen Neuzil ³ , Vanessa Raabe ^{1 2} , Ruth Bailey ⁴ , Kena A Swanson ⁶ , Ping Li ⁷ , Kenneth Koury ⁶ , Warren Kalina ⁶ , David Cooper ⁶ , Camila Fontes-Garfias ⁸ , Pei-Yong Shi ⁸ , ?zlem T?reci ⁹ , Kristin R Tompkins ⁶ , Edward E Walsh ^{10 11} , Robert Frenck ¹² , Ann R Falsey ^{10 11} , Philip R Dormitzer ⁶ , William C Gruber ⁶ , Uğur Şahin ⁹ , Kathrin U Jansen ⁶



Affiliations

• PMID: 32785213
• DOI: 10.1038/s41586-020-2639-4

Abstract

In March 2020, the World Health Organization (WHO) declared a pandemic of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)¹. With rapidly accumulating cases and deaths reported globally², a vaccine is urgently needed. We report the available safety, tolerability, and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose escalation study among 45 healthy adults, 18 to 55 years of age, randomized to receive 2 doses, separated by 21 days, of 10 ?g, 30 ?g, or 100 ?g of BNT162b1, a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD). Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100 ?g was not administered due to increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared to the 30 μg dose. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titers in sera increased with dose level and after a second dose. Geometric mean neutralizing titers reached 1.9- to 4.6-fold that of a panel of COVID-19 convalescent human sera at least 14 days after a positive SARS-CoV-2 PCR. These results support further evaluation of this mRNA vaccine candidate. (ClinicalTrials.gov identifier: NCT04368728).