Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus
Jason S. McLellan,Man Chen,M. Gordon Joyce,Mallika Sastry,Guillaume Stewart-Jones,Yongping Yang,Baoshan Zhang,Lei Chen,Sanjay Srivatsan,Anqi Zheng,Tongqing Zhou,Kevin W. Graepel,Azad Kumar,Syed M. Moin,Jeffrey C. Boyington,Gwo-Yu Chuang,Cinque Soto,Ulrich Baxa,Arjen Q. Bakker,Hergen Spits,Tim Beaumont,Zizheng Zheng,Ningshao Xia,Sung Youl Ko,John Paul Todd,Srinivas S. Rao,Barney S. Graham,Peter D. Kwong +27 more
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TLDR
A viral antigen is sought that provides greater protection than currently available vaccines and focused on antigenic site Ø, a metastable site specific to the prefusion state of the RSV fusion (F) glycoprotein, as this site is targeted by extremely potent RSV-neutralizing antibodies.Abstract:
Respiratory syncytial virus (RSV) is the leading cause of hospitalization for children under 5 years of age. We sought to engineer a viral antigen that provides greater protection than currently available vaccines and focused on antigenic site O, a metastable site specific to the prefusion state of the RSV fusion (F) glycoprotein, as this site is targeted by extremely potent RSV-neutralizing antibodies. Structure-based design yielded stabilized versions of RSV F that maintained antigenic site O when exposed to extremes of pH, osmolality, and temperature. Six RSV F crystal structures provided atomic-level data on how introduced cysteine residues and filled hydrophobic cavities improved stability. Immunization with site O–stabilized variants of RSV F in mice and macaques elicited levels of RSV-specific neutralizing activity many times the protective threshold.read more
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Journal ArticleDOI
The Respiratory Syncytial Virus (RSV) G Protein Enhances the Immune Responses to the RSV F Protein in an Enveloped Virus-Like Particle Vaccine Candidate
TL;DR: In this article , the authors proposed a vaccine for respiratory syncytial virus (RSV) in infants, young children, and the elderly, which is a priority for developing an effective vaccine for these populations.
Dissertation
Structural and stability studies on domain IV of anthrax toxin protective antigen (PA); its role in anthrax pathogenesis
TL;DR: Thesis (Ph.D.) as mentioned in this paper, Wichita State University, College of Liberal Arts and Sciences, Dept. of Chemistry (CLAS), WSU, Wichita, KS.
Patent
Novel recombinant prefusion rsv f proteins and uses thereof
TL;DR: In this paper, the authors provided immunogens comprising a recombinant Respiratory Syncytial Virus (RSV) F protein stabilized in a prefusion conformation and nucleic acids encoding such immunogens.
Journal ArticleDOI
Subnanometer structure of an enveloped virus fusion complex on viral surface reveals new entry mechanisms
Tara C. Marcink,Gillian Zipursky,Wenjing Cheng,Kyle N. Stearns,Shari Stenglein,Kate L Golub,Frances Cohen,Francesca T. Bovier,Daniel L. Pfalmer,Alexander L. Greninger,Matteo Porotto,Amedee des Georges,Anne Moscona +12 more
TL;DR: In this article , the authors used cryo-electron tomography to visualize the fusion complex of human parainfluenza virus 3 (HN/F) on the surface of authentic clinical viruses at sub-nanometer resolution.
Combination nanovaccines against respiratory pathogens
TL;DR: These pathogens are highly lethal if inhaled, with mortality rates approaching 100% if untreated after only a few days, and both of these pathogens have been used as biological weapons to cause harm to civilians and military personnel, with the most recent being the 9/11 attacks in the United States in 2001.
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TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2010 aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex, using the Cause of Death Ensemble model.
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