Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults.
Mark J. Mulligan,Kirsten E. Lyke,Nicholas Kitchin,Judith Absalon,Alejandra Gurtman,Stephen Lockhart,Kathleen M. Neuzil,Vanessa Raabe,Ruth Bailey,Kena A. Swanson,Ping Li,Kenneth Koury,Warren Kalina,David A. Cooper,Camila R. Fontes-Garfias,Pei Yong Shi,Özlem Türeci,Tompkins Kristin Rachael,Edward E. Walsh,Edward E. Walsh,Robert W. Frenck,Ann R. Falsey,Ann R. Falsey,Philip R. Dormitzer,William C. Gruber,Ugur Sahin,Kathrin U. Jansen +26 more
TLDR
In a dose-escalation study of the COVID-19 RNA vaccine BNT162b1 in 45 healthy adults, RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second vaccine dose.Abstract:
In March 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1, a pandemic. With rapidly accumulating numbers of cases and deaths reported globally2, a vaccine is urgently needed. Here we report the available safety, tolerability and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose-escalation study (ClinicalTrials.gov identifier NCT04368728) among 45 healthy adults (18–55 years of age), who were randomized to receive 2 doses—separated by 21 days—of 10 μg, 30 μg or 100 μg of BNT162b1. BNT162b1 is a lipid-nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes the trimerized receptor-binding domain (RBD) of the spike glycoprotein of SARS-CoV-2. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100 μg was not administered because of the increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared with the 30-μg dose. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second dose. Geometric mean neutralizing titres reached 1.9–4.6-fold that of a panel of COVID-19 convalescent human sera, which were obtained at least 14 days after a positive SARS-CoV-2 PCR. These results support further evaluation of this mRNA vaccine candidate. In a dose-escalation study of the COVID-19 RNA vaccine BNT162b1 in 45 healthy adults, RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second vaccine dose.read more
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Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates.
Edward E. Walsh,Robert W. Frenck,Ann R. Falsey,Ann R. Falsey,Nicholas Kitchin,Judith Absalon,Alejandra Gurtman,Stephen Lockhart,Kathleen M. Neuzil,Mark J. Mulligan,Ruth Bailey,Kena A. Swanson,Ping Li,Kenneth Koury,Warren Kalina,David A. Cooper,Camila R. Fontes-Garfias,Pei Yong Shi,Özlem Türeci,Tompkins Kristin Rachael,Kirsten E. Lyke,Vanessa Raabe,Philip R. Dormitzer,Kathrin U. Jansen,Ugur Sahin,William C. Gruber +25 more
TL;DR: The safety and immunogenicity data from this U.S. phase 1 trial of two vaccine candidates in younger and older adults support the selection of BNT162b2 for advancement to a pivotal phase 2–3 safety and efficacy evaluation.
Journal ArticleDOI
SARS-CoV-2 vaccines in development.
TL;DR: The development of vaccines against SARS-CoV-2 is reviewed, including an overview of the development process, the different types of vaccine candidate, and data from animal studies as well as phase I and II clinical trials in humans.
Journal ArticleDOI
COVID-19 vaccine BNT162b1 elicits human antibody and T H 1 T cell responses.
Ugur Sahin,Alexander Muik,Evelyna Derhovanessian,Isabel Vogler,Lena M. Kranz,Mathias Vormehr,Alina Baum,Kristen E. Pascal,Jasmin Quandt,Daniel Maurus,Sebastian Brachtendorf,Verena Lörks,Julian Sikorski,Rolf Hilker,Dirk Becker,Ann Kathrin Eller,Jan Grützner,Carsten Boesler,Corinna Rosenbaum,Marie Cristine Kühnle,Ulrich Luxemburger,Alexandra Kemmer-Brück,David J. Langer,Martin Bexon,Stefanie Bolte,Katalin Karikó,Tania Palanche,Boris Fischer,Armin Schultz,Pei Yong Shi,Camila R. Fontes-Garfias,John L. Perez,Kena A. Swanson,Jakob Loschko,Ingrid L. Scully,Mark Cutler,Warren Kalina,Christos A. Kyratsous,David A. Cooper,Philip R. Dormitzer,Kathrin U. Jansen,Özlem Türeci +41 more
TL;DR: The robust RBD-specific antibody, T cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest that it has the potential to protect against COVID-19 through multiple beneficial mechanisms.
Journal ArticleDOI
Spike mutation D614G alters SARS-CoV-2 fitness.
Jessica A. Plante,Yang Liu,Jianying Liu,Hongjie Xia,Bryan A. Johnson,Kumari G. Lokugamage,Xianwen Zhang,Antonio E. Muruato,Jing Zou,Camila R. Fontes-Garfias,Divya Mirchandani,Dionna Scharton,John P. Bilello,Zhiqiang Ku,Zhiqiang An,Birte Kalveram,Alexander N. Freiberg,Vineet D. Menachery,Xuping Xie,Kenneth S. Plante,Scott C. Weaver,Pei Yong Shi +21 more
TL;DR: Hamsters infected with SARS-CoV-2 expressing spike D614G (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission.
Journal ArticleDOI
Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data.
Eric J. Haas,Eric J. Haas,Frederick J. Angulo,John M McLaughlin,Emilia Anis,Emilia Anis,Shepherd Roee Singer,Shepherd Roee Singer,Farid Khan,Nati Brooks,Meir Smaja,Gabriel Mircus,Kaijie Pan,Jo Southern,David L. Swerdlow,Luis Jodar,Yeheskel Levy,Sharon Alroy-Preis +17 more
TL;DR: In this article, the real-world effectiveness of two doses of BNT162b2 against a range of SARS-CoV-2 outcomes and to evaluate the nationwide public-health impact following the widespread introduction of the vaccine was estimated.
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TL;DR: It is found that mRNAs containing pseudouridines have a higher translational capacity than unmodified m RNAs when tested in mammalian cells and lysates or administered intravenously into mice at 0.015-0.15 mg/kg doses.
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