SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness

被引:358
作者
Corbett, Kizzmekia S. [1 ]
Edwards, Darin K. [2 ]
Leist, Sarah R. [3 ]
Abiona, Olubukola M. [1 ]
Boyoglu-Barnum, Seyhan [1 ]
Gillespie, Rebecca A. [1 ]
Himansu, Sunny [2 ]
Schafer, Alexandra [3 ]
Ziwawo, Cynthia T. [1 ]
DiPiazza, Anthony T. [1 ]
Dinnon, Kenneth H. [3 ]
Elbashir, Sayda M. [2 ]
Shaw, Christine A. [2 ]
Woods, Angela [2 ]
Fritch, Ethan J. [4 ]
Martinez, David R. [3 ]
Bock, Kevin W. [5 ]
Minai, Mahnaz [5 ]
Nagata, Bianca M. [5 ]
Hutchinson, Geoffrey B. [1 ]
Wu, Kai [2 ]
Henry, Carole [2 ]
Bahl, Kapil
Garcia-Dominguez, Dario [2 ]
Ma, LingZhi [2 ]
Renzi, Isabella [2 ]
Kong, Wing-Pui [1 ]
Schmidt, Stephen D. [1 ]
Wang, Lingshu [1 ]
Zhang, Yi [1 ]
Phung, Emily [1 ,6 ]
Chang, Lauren A. [1 ]
Loomis, Rebecca J. [1 ]
Altaras, Nedim Emil [2 ]
Narayanan, Elisabeth [2 ]
Metkar, Mihir [2 ]
Presnyak, Vlad [2 ]
Liu, Cuiping [1 ]
Louder, Mark K. [1 ]
Shi, Wei [1 ]
Leung, Kwanyee [1 ]
Yang, Eun Sung [1 ]
West, Ande [3 ]
Gully, Kendra L. [3 ]
Stevens, Laura J. [7 ]
Gully, Kendra L. [3 ]
Wang, Nianshuang [8 ]
Wrapp, Daniel [8 ]
Doria-Rose, Nicole A. [1 ]
Stewart-Jones, Guillaume [2 ]
机构
[1] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[2] Moderna Inc, Cambridge, MA USA
[3] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27515 USA
[4] Univ N Carolina, Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC 27515 USA
[5] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[6] George Washington Univ, Inst Biomed Sci, Washington, DC USA
[7] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA
[8] Univ Texas Austin, Dept Mol Biosci, Austin, TX 78712 USA
[9] NIAID, Biostat Res Branch, Div Clin Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
关键词
MERS-COV; SPIKE; INFLUENZA; IMMUNOGENICITY; PROTECTION; VIRUS; RSV;
D O I
10.1038/s41586-020-2622-0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 immunogenicity(1). 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 mutant(2) 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.
引用
收藏
页码:567 / +
页数:21
相关论文
共 43 条
  • [1] Adenovirus vector-induced innate inflammatory mediators, MAPK signaling, as well as adaptive immune responses are dependent upon both TLR2 and TLR9 in vivo
    Appledorn, Daniel M.
    Patial, Sonika
    McBride, Aaron
    Godbehere, Sarah
    Van Rooijen, Nico
    Parameswaran, Narayanan
    Amalfitano, Andrea
    [J]. JOURNAL OF IMMUNOLOGY, 2008, 181 (03) : 2134 - 2144
  • [2] Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses
    Bahl, Kapil
    Senn, Joe J.
    Yuzhakov, Olga
    Bulychev, Alex
    Brito, Luis A.
    Hassett, Kimberly J.
    Laska, Michael E.
    Smith, Mike
    Almarsson, Orn
    Thompson, James
    Ribeiro, Amilcar
    Watson, Mike
    Zaks, Tal
    Ciaramella, Giuseppe
    [J]. MOLECULAR THERAPY, 2017, 25 (06) : 1316 - 1327
  • [3] A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response
    Bolles, Meagan
    Deming, Damon
    Long, Kristin
    Agnihothram, Sudhakar
    Whitmore, Alan
    Ferris, Martin
    Funkhouser, William
    Gralinski, Lisa
    Totura, Allison
    Heise, Mark
    Baric, Ralph S.
    [J]. JOURNAL OF VIROLOGY, 2011, 85 (23) : 12201 - 12215
  • [4] Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT from human airway epithelium
    Böttcher, Eva
    Matrosovich, Tatyana
    Beyerle, Michaela
    Klenk, Hans-Dieter
    Garten, Wolfgang
    Matrosovich, Mikhail
    [J]. JOURNAL OF VIROLOGY, 2006, 80 (19) : 9896 - 9898
  • [5] A mouse model for MERS coronavirus-induced acute respiratory distress syndrome
    Cockrell, Adam S.
    Yount, Boyd L.
    Scobey, Trevor
    Jensen, Kara
    Douglas, Madeline
    Beall, Anne
    Tang, Xian-Chun
    Marasco, Wayne A.
    Heise, Mark T.
    Baric, Ralph S.
    [J]. NATURE MICROBIOLOGY, 2017, 2 (02):
  • [6] A proof of concept for structure-based vaccine design targeting RSV in humans
    Crank, Michelle C.
    Ruckwardt, Tracy J.
    Chen, Man
    Morabito, Kaitlyn M.
    Phung, Emily
    Costner, Pamela J.
    Holman, LaSonji A.
    Hickman, Somia P.
    Berkowitz, Nina M.
    Gordon, Ingelise J.
    Yamshchikov, Galina V.
    Gaudinski, Martin R.
    Kumar, Azad
    Chang, Lauren A.
    Moin, Syed M.
    Hill, Juliane P.
    DiPiazza, Anthony T.
    Schwartz, Richard M.
    Kueltzo, Lisa
    Cooper, Jonathan W.
    Chen, Peifeng
    Stein, Judith A.
    Carlton, Kevin
    Gall, Jason G.
    Nason, Martha C.
    Kwong, Peter D.
    Chen, Grace L.
    Mascola, John R.
    McLellan, Jason S.
    Ledgerwood, Julie E.
    Graham, Barney S.
    [J]. SCIENCE, 2019, 365 (6452) : 505 - +
  • [7] Evaluation of modified vaccinia virus Ankara based recombinant SARS vaccine in ferrets
    Czub, M
    Weingartl, H
    Czub, S
    He, RT
    Cao, JX
    [J]. VACCINE, 2005, 23 (17-18) : 2273 - 2279
  • [8] Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing epidemic and zoonotic spike variants
    Deming, Damon
    Sheahan, Timothy
    Heise, Mark
    Yount, Boyd
    Davis, Nancy
    Sims, Amy
    Suthar, Mehul
    Harkema, Jack
    Whitmore, Alan
    Pickles, Raymond
    West, Ande
    Donaldson, Eric
    Curtis, Kristopher
    Johnston, Robert
    Baric, Ralph
    [J]. PLOS MEDICINE, 2006, 3 (12) : 2359 - 2375
  • [9] A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures
    Dinnon, Kenneth H., III
    Leist, Sarah R.
    Schafer, Alexandra
    Edwards, Caitlin E.
    Martinez, David R.
    Montgomery, Stephanie A.
    West, Ande
    Yount, Boyd L., Jr.
    Hou, Yixuan J.
    Adams, Lily E.
    Gully, Kendra L.
    Brown, Ariane J.
    Huang, Emily
    Bryant, Matthew D.
    Choong, Ingrid C.
    Glenn, Jeffrey S.
    Gralinski, Lisa E.
    Sheahan, Timothy P.
    Baric, Ralph S.
    [J]. NATURE, 2020, 586 (7830) : 560 - +
  • [10] An interactive web-based dashboard to track COVID-19 in real time
    Dong, Ensheng
    Du, Hongru
    Gardner, Lauren
    [J]. LANCET INFECTIOUS DISEASES, 2020, 20 (05) : 533 - 534