Compared to vaccination with the soluble SARS-CoV-2 Spike protein, on which numerous leading COVID-19 vaccine candidates are based, the new nanoparticle vaccine produced 10 times more reducing the effects of antibodies in mice, even at a sixfold lower dosage. When administered to a single nonhuman primate, the nanoparticle vaccine produced reducing the effects of antibodies targeting numerous different sites on the Spike protein.
Recommendation: “Elicitation of potent neutralizing antibody reactions by developed protein nanoparticle vaccines for SARS-CoV-2Alexandra C. Walls, Brooke Fiala, Alexandra Schäfer, Samuel Wrenn, Minh N. Pham, Michael Murphy, Longping V. Tse, Laila Shehata, Megan A. OConnor, Chengbo Chen, Mary Jane Navarro, Marcos C. Miranda, Deleah Pettie, Rashmi Ravichandran, John C. Kraft, Cassandra Ogohara, Anne Palser, Sara Chalk, E-Chiang Lee, Kathryn Guerriero, Elizabeth Kepl, Cameron M. Chow, Claire Sydeman, Edgar A. Hodge, Brieann Brown, Jim T. Fuller, Kenneth H. Dinnon, III, Lisa E. Gralinski, Sarah R. Leist, Kendra L. Gully, Thomas B. Lewis, Miklos Guttman, Helen Y. Chu, Kelly K. Lee, Deborah H. Fuller, Ralph S. Baric, Paul Kellam, Lauren Carter, Marion Pepper, Timothy P. Sheahan, David Veesler and Neil P. King, Accepted 26 October 2020, Cell.DOI: 10.1016/ j.cell.2020.10.043.
The research reported in Cell was supported by the National Institute of Allergy and Infectious Diseases (DP1AI158186, HHSN272201700059C, 3U01AI42001-02S1), National Institute of General Medical Sciences (R01GM120553, R01GM099989), Bill & & Melinda Gates Foundation (OPP1156262, OPP1126258, OPP1159947), Defense Threat Reduction Agency (HDTRA1-18-1-0001), Pew Biomedical Scholars Award, Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund, Fast Grants, Animal Models Contract HHSN272201700036I-75N93020F00001, University of Washingtons Proteomics Resource (UWPR95794), North Carolina Coronavirus Relief Fund, and presents from Jodi Green and Mike Halperin and from The Audacious Project.
An ingenious nanoparticle vaccine candidate for the pandemic coronavirus produces virus-neutralizing antibodies in mice at levels 10 times higher than is seen in individuals who have recovered from COVID-19 infections. Designed by researchers at the University of Washington School of Medicine in Seattle, the vaccine prospect has been transferred to two business for medical development.
The vaccine candidate was developed utilizing structure-based vaccine style strategies created at UW Medicine. It is a self-assembling protein nanoparticle that shows 60 copies of the SARS-CoV-2 Spike proteins receptor-binding domain in a highly immunogenic selection. The molecular structure of the vaccine roughly mimics that of a virus, which may represent its boosted ability to provoke an immune response.
Artists representation of an ultrapotent COVID-19 vaccine candidate in which 60 pieces of a coronavirus protein (red) decorate nanoparticles (blue and white). The molecular structure of the vaccine approximately mimics that of an infection, which might account for its enhanced capability to provoke an immune action.
Hundreds of candidate vaccines for COVID-19 are in development around the world. Lots of need large dosages, intricate production, and cold-chain shipping and storage. An ultrapotent vaccine that is safe, effective at low doses, simple to produce and steady beyond a freezer might make it possible for vaccination against COVID-19 on an international scale.
” We hope that our nanoparticle platform might assist combat this pandemic that is triggering a lot damage to our world,” said King, creator of the computational vaccine style technology at the Institute for Protein Design. “The potency, stability, and manufacturability of this vaccine prospect differentiate it from many others under investigation.”.
Preclinical data published in Cell show the nanoparticle vaccine stimulates extremely high levels of protective antibodies in animal designs.
Artists depiction of an ultrapotent COVID-19 vaccine candidate in which 60 pieces of a coronavirus protein (red) decorate nanoparticles (blue and white). Compared to vaccination with the soluble SARS-CoV-2 Spike protein, on which many leading COVID-19 vaccine prospects are based, the brand-new nanoparticle vaccine produced 10 times more neutralizing antibodies in mice, even at a sixfold lower dosage. When administered to a single nonhuman primate, the nanoparticle vaccine produced neutralizing antibodies targeting multiple different sites on the Spike protein. Production schematic programs how coronavirus proteins are added to a computer-designed nanoparticle platform to produce a candidate vaccine versus COVID-19. The vaccine prospect was created and evaluated in animal models by scientists at the University of Washington School of Medicine.
Production schematic demonstrate how coronavirus proteins are contributed to a computer-designed nanoparticle platform to create a candidate vaccine versus COVID-19. The vaccine prospect was created and evaluated in animal designs by researchers at the University of Washington School of Medicine. Credit: Ian Haydon/UW Medicine Institute for Protein Design.
” I am happy that our research studies of antibody actions to coronaviruses led to the style of this promising vaccine prospect,” said Veesler, who led the concept of a multivalent, receptor-binding, domain-based vaccine.
The lead vaccine candidate from this report is being licensed non-exclusively and royalty-free throughout the pandemic by the University of Washington. One licensee, Icosavax, a Seattle biotechnology company co-founded in 2019 by King, is currently advancing research studies to support regulatory filings and has actually started the U.S. Food and Drug Administrations Good Manufacturing Practice. To accelerate progress by Icosavax to the clinic, Amgen has accepted manufacture a key intermediate for these preliminary scientific research studies. Another licensee, SK bioscience of South Korea, is advancing its own studies to support clinical and additional advancement..
The findings were released on October 30, 2020, in Cell. The lead authors of this paper are Alexandra Walls, a research study researcher in the lab of David Veesler, a UW associate professor of biochemistry; and Brooke Fiala, a research study researcher in the lab of Neil King, UW assistant teacher of biochemistry.