Yeast-Expressed SARS-CoV Recombinant Receptor-Binding Domain (RBD219-N1) Formulated with Alum Induces Protective Immunity and Reduces Immune Enhancement
Wen-Hsiang Chen,Wen-Hsiang Chen,Xinrong Tao,Xinrong Tao,Anurodh S. Agrawal,Abdullah Algaissi,Bi Hung Peng,Jeroen Pollet,Jeroen Pollet,Ulrich Strych,Ulrich Strych,Maria Elena Bottazzi,Peter J. Hotez,Sara Lustigman,Lanying Du,Shibo Jiang,Chien-Te K Tseng +16 more
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TLDR
It is reported that mice immunized with RBD219-N1/Alhydrogel® were fully protected from lethal SARS-CoV challenge (0% mortality), compared to ∼ 30% mortality in mice when immunizing with the SARS S protein formulated with AlHydrogel®, and 100% mortality with non-detectable viral loads with minimal or no eosinophilic pulmonary infiltrates.Abstract:
We developed a severe acute respiratory syndrome (SARS) subunit recombinant protein vaccine candidate based on a high-yielding, yeast-engineered, receptor-binding domain (RBD219-N1) of the SARS beta-coronavirus (SARS-CoV) spike (S) protein. When formulated with Alhydrogel®, RBD219-N1 induced high-level neutralizing antibodies against both pseudotyped virus and a clinical (mouse-adapted) isolate of SARS-CoV. Here, we report that mice immunized with RBD219-N1/Alhydrogel® were fully protected from lethal SARS-CoV challenge (0% mortality), compared to ∼ 30% mortality in mice when immunized with the SARS S protein formulated with Alhydrogel®, and 100% mortality in negative controls. An RBD219-N1 formulation Alhydrogel® was also superior to the S protein, unadjuvanted RBD, and AddaVax (MF59-like adjuvant)-formulated RBD in inducing specific antibodies and preventing cellular infiltrates in the lungs upon SARS-CoV challenge. Specifically, a formulation with a 1:25 ratio of RBD219-N1 to Alhydrogel® provided high neutralizing antibody titers, 100% protection with non-detectable viral loads with minimal or no eosinophilic pulmonary infiltrates. As a result, this vaccine formulation is under consideration for further development against SARS-CoV and other emerging and re-emerging beta-CoVs such as SARS-CoV-2.read more
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Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding.
Tyler N. Starr,Allison J. Greaney,Allison J. Greaney,Sarah K Hilton,Sarah K Hilton,Daniel Ellis,Katharine H.D. Crawford,Katharine H.D. Crawford,Adam S. Dingens,Mary Jane Navarro,John E. Bowen,M. Alejandra Tortorici,Alexandra C. Walls,Neil P. King,David Veesler,Jesse D. Bloom,Jesse D. Bloom,Jesse D. Bloom +17 more
TL;DR: It is found that a substantial number of mutations to the RBD are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses.
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
The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens.
TL;DR: This review highlights and describes the recent progress that has been made in the biosynthesis, structure, function, and antigenicity of the SARS-CoV-2 S glycoprotein, aiming to provide valuable insights into the design and development ofThe S protein-based vaccines as well as therapeutics.
Posted ContentDOI
Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding.
Tyler N. Starr,Allison J. Greaney,Allison J. Greaney,Sarah K Hilton,Sarah K Hilton,Katharine H.D. Crawford,Katharine H.D. Crawford,Mary Jane Navarro,John E. Bowen,M. Alejandra Tortorici,Alexandra C. Walls,David Veesler,Jesse D. Bloom,Jesse D. Bloom,Jesse D. Bloom +14 more
TL;DR: An interactive visualization and open analysis pipeline is presented to facilitate use of the dataset for vaccine design and functional annotation of mutations observed during viral surveillance.
Journal ArticleDOI
Prospects for a safe COVID-19 vaccine.
Barton F. Haynes,Lawrence Corey,Prabhavathi Fernandes,Peter B. Gilbert,Peter J. Hotez,Srinivas S. Rao,Michael R. Santos,Hanneke Schuitemaker,Michael Watson,Ann M. Arvin +9 more
TL;DR: Evaluated research on the potential risk of immune enhancement of disease by vaccines and viral infections, including coronavirus infections, together with emerging data about COVID-19 disease finds neither principles of immunity nor preclinical studies provide a basis for prioritizing among the CO VID-19 vaccine candidates with respect to safety.
References
More filters
Journal ArticleDOI
Isolation of a Novel Coronavirus from a Man with Pneumonia in Saudi Arabia
Ali Moh Zaki,Sander van Boheemen,Theo M. Bestebroer,Albert D. M. E. Osterhaus,Ron A. M. Fouchier +4 more
TL;DR: The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
Journal ArticleDOI
Identification of a novel coronavirus in patients with severe acute respiratory syndrome.
Christian Drosten,Stephan Günther,Wolfgang Preiser,Sylvie van der Werf,H. R. Brodt,Stephan Becker,Holger F. Rabenau,Marcus Panning,Larissa Kolesnikova,Ron A. M. Fouchier,Annemarie Berger,Ana-Maria Burguière,Jindrich Cinatl,Markus Eickmann,Nicolas Escriou,Klaus Grywna,Stefanie Kramme,Jean-Claude Manuguerra,Stefanie Müller,Volker Rickerts,Martin Stürmer,Simon Vieth,Hans-Dieter Klenk,Albert D. M. E. Osterhaus,Herbert Schmitz,Hans Wilhelm Doerr +25 more
TL;DR: The novel coronavirus might have a role in causing SARS and was detected in a variety of clinical specimens from patients with SARS but not in controls.
Journal ArticleDOI
A novel coronavirus associated with severe acute respiratory syndrome.
Thomas G. Ksiazek,Dean D. Erdman,Cynthia S. Goldsmith,Zaki,Teresa C. T. Peret,Shannon L. Emery,Suxiang Tong,Urbani C,James A. Comer,Wilina Lim,Pierre E. Rollin,Scott F. Dowell,Ai Ee Ling,Charles D. Humphrey,Wun-Ju Shieh,Jeannette Guarner,Christopher D. Paddock,Paul A. Rota,Barry S. Fields,Joseph L. DeRisi,Jyh-Yuan Yang,Nancy J. Cox,James M. Hughes,James W. LeDuc,William J. Bellini,Larry J. Anderson +25 more
TL;DR: A novel coronavirus is associated with this outbreak of severe acute respiratory syndrome, and the evidence indicates that this virus has an etiologic role in SARS.
Journal ArticleDOI
The spike protein of SARS-CoV — a target for vaccine and therapeutic development
TL;DR: Recent advances in the development of vaccines and therapeutics based on the S protein are highlighted, which plays key parts in the induction of neutralizing-antibody and T-cell responses, as well as protective immunity, during infection with SARS-CoV.
Journal ArticleDOI
Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003
Nanshan Zhong,Bo-Jian Zheng,Yimin Li,Leo L.M. Poon,Z. H. Xie,KH Chan,Philip H. Li,S. Y. Tan,Qingsong Chang,J. P. Xie,X. Q. Liu,J. Xu,D. X. Li,Kwok-Yung Yuen,Joseph S. M. Peiris,Yi Guan +15 more
TL;DR: Genetic analysis showed that the SARS CoV isolates from Guangzhou shared the same origin with those in other countries, and had a phylogenetic pathway that matched the spread of SARS to the other parts of the world.
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