SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness.
Kizzmekia S. Corbett,Darin K. Edwards,Sarah R. Leist,Olubukola M. Abiona,Seyhan Boyoglu-Barnum,Rebecca A. Gillespie,Sunny Himansu,Alexandra Schäfer,Cynthia T. Ziwawo,Anthony T. DiPiazza,Kenneth H. Dinnon,Sayda Elbashir,Christine A. Shaw,Angela Woods,Ethan J. Fritch,David R. Martinez,Kevin W. Bock,Mahnaz Minai,Bianca M. Nagata,Geoffrey B. Hutchinson,Kai Wu,Carole Henry,Kapil Bahl,Dario Garcia-Dominguez,Ling Zhi Ma,Isabella Renzi,Wing Pui Kong,Stephen D. Schmidt,Lingshu Wang,Yi Zhang,Emily Phung,Emily Phung,Lauren A. Chang,Rebecca J. Loomis,Nedim Emil Altaras,Elisabeth Narayanan,Mihir Metkar,Vlad Presnyak,Cuiping Liu,Mark K. Louder,Wei Shi,Kwanyee Leung,Eun Sung Yang,Ande West,Kendra Gully,Laura J. Stevens,Nianshuang Wang,Daniel Wrapp,Nicole A. Doria-Rose,Guillaume Stewart-Jones,Hamilton Bennett,Gabriela S. Alvarado,Martha Nason,Tracy J. Ruckwardt,Jason S. McLellan,Mark R. Denison,James D. Chappell,Ian N. Moore,Kaitlyn M. Morabito,John R. Mascola,Ralph S. Baric,Andrea Carfi,Barney S. Graham +62 more
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In this article, an mRNA vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is proposed, which is used to control the CoVID-19 global pandemic.Abstract:
A vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to control the coronavirus disease 2019 (COVID-19) global pandemic. Structural studies have led to the development of mutations that stabilize Betacoronavirus spike proteins in the prefusion state, improving their expression and increasing immunogenicity1. This principle has been applied to design mRNA-1273, an mRNA vaccine that encodes a SARS-CoV-2 spike protein that is stabilized in the prefusion conformation. Here we show that mRNA-1273 induces potent neutralizing antibody responses to both wild-type (D614) and D614G mutant2 SARS-CoV-2 as well as CD8+ T cell responses, and protects against SARS-CoV-2 infection in the lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a phase III trial to evaluate its efficacy.read more
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Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine.
Lindsey R. Baden,Hana M. El Sahly,Brandon Essink,Karen L. Kotloff,Sharon E. Frey,Rick Novak,David Diemert,Stephen A. Spector,Nadine Rouphael,C. Buddy Creech,John W McGettigan,Shishir Khetan,Nathan Segall,Joel Solis,Adam Brosz,Carlos Fierro,Howard J. Schwartz,Kathleen M. Neuzil,Lawrence Corey,Peter B. Gilbert,Holly Janes,Dean Follmann,Mary A. Marovich,John R. Mascola,Laura Polakowski,Julie E. Ledgerwood,Barney S. Graham,Hamilton Bennett,Rolando Pajon,Conor Knightly,Brett Leav,Weiping Deng,Honghong Zhou,Shu Liang Han,Melanie Ivarsson,Jacqueline Miller,Tal Z Zaks +36 more
TL;DR: The mRNA-1273 vaccine as discussed by the authors is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.
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
Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults.
Evan J. Anderson,Nadine Rouphael,Alicia T. Widge,Lisa A. Jackson,Paul C. Roberts,Mamodikoe Makhene,James D. Chappell,Mark R. Denison,Laura J. Stevens,Andrea J. Pruijssers,Adrian B. McDermott,Britta Flach,Bob C. Lin,Nicole A. Doria-Rose,Sijy O'Dell,Stephen D. Schmidt,Kizzmekia S. Corbett,Phillip A. Swanson,Marcelino Padilla,Kathy M. Neuzil,Hamilton Bennett,Brett A. Leav,Mat Makowski,Jim Albert,Kaitlyn Cross,Venkata Viswanadh Edara,Katharine Floyd,Mehul S. Suthar,David R. Martinez,Ralph S. Baric,Wendy Buchanan,Catherine J. Luke,Varun K Phadke,Christina A. Rostad,Julie E. Ledgerwood,Barney S. Graham,John H. Beigel +36 more
TL;DR: The phase 1, dose-escalation, open-label trial of a messenger RNA vaccine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein in healthy adults found it induced higher binding- and neutralizing-antibody titers than the 25-μg dose, which supports the use of the 100- μg dose in a phase 3 vaccine trial.
Journal ArticleDOI
Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates.
Kizzmekia S. Corbett,Barbara J. Flynn,Kathryn E. Foulds,Joseph R. Francica,Seyhan Boyoglu-Barnum,Anne P. Werner,Britta Flach,Sarah O’Connell,Kevin W. Bock,Mahnaz Minai,Bianca M. Nagata,Hanne Leth Andersen,David R. Martinez,Amy T. Noe,Naomi Douek,Mitzi M. Donaldson,Nadesh N Nji,Gabriela S. Alvarado,Darin K. Edwards,Dillon R. Flebbe,Evan Lamb,Nicole A. Doria-Rose,Bob C. Lin,Mark K. Louder,Sijy O'Dell,Stephen D. Schmidt,Emily Phung,Lauren A. Chang,Christina Yap,John-Paul Todd,Laurent Pessaint,Alex Van Ry,Shanai Browne,Jack Greenhouse,Tammy Putman-Taylor,Amanda Strasbaugh,Tracey-Ann Campbell,Anthony Cook,Alan Dodson,Katelyn Steingrebe,Wei Shi,Yi Zhang,Olubukola M. Abiona,Lingshu Wang,Amarendra Pegu,Eun Sung Yang,Kwanyee Leung,Tongqing Zhou,I-Ting Teng,Alicia T. Widge,Ingelise J. Gordon,Laura Novik,Rebecca A. Gillespie,Rebecca J. Loomis,Juan I. Moliva,Guillaume Stewart-Jones,Sunny Himansu,Wing-Pui Kong,Martha Nason,Kaitlyn M. Morabito,Tracy J. Ruckwardt,Julie E. Ledgerwood,Martin R. Gaudinski,Peter D. Kwong,John R. Mascola,Andrea Carfi,Mark G. Lewis,Ralph S. Baric,Adrian B. McDermott,Ian N. Moore,Nancy J. Sullivan,Mario Roederer,Robert A. Seder,Barney S. Graham +73 more
TL;DR: Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung.
Journal ArticleDOI
Immunological considerations for COVID-19 vaccine strategies.
Mangalakumari Jeyanathan,Sam Afkhami,Fiona Smaill,Matthew S. Miller,Brian D. Lichty,Zhou Xing +5 more
TL;DR: The immunological principles that need to be taken into consideration in the development of COVID-19 vaccine strategies are discussed and their strengths and potential shortfalls are examined, and inferences about their chances of success are made.
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Lisa A. Jackson,Evan J. Anderson,Nadine Rouphael,Paul C. Roberts,Mamodikoe Makhene,Rhea N. Coler,Michele Paine McCullough,James D. Chappell,Mark R. Denison,Laura J. Stevens,Andrea J. Pruijssers,Adrian B. McDermott,Britta Flach,Nicole A. Doria-Rose,Kizzmekia S. Corbett,Kaitlyn M. Morabito,Sijy O’Dell,Stephen D. Schmidt,Phillip A. Swanson,Marcelino Padilla,John R. Mascola,Kathleen M. Neuzil,Hamilton Bennett,Wellington Sun,Etza Peters,Mat Makowski,Jim Albert,Kaitlyn Cross,Wendy Buchanan,Rhonda Pikaart-Tautges,Julie E. Ledgerwood,Barney S. Graham,John H. Beigel +32 more
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mRNA vaccines — a new era in vaccinology
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