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Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate.
Bangaru, Sandhya; Ozorowski, Gabriel; Turner, Hannah L; Antanasijevic, Aleksandar; Huang, Deli; Wang, Xiaoning; Torres, Jonathan L; Diedrich, Jolene K; Tian, Jing-Hui; Portnoff, Alyse D; Patel, Nita; Massare, Michael J; Yates, John R; Nemazee, David; Paulson, James C; Glenn, Greg; Smith, Gale; Ward, Andrew B.
  • Bangaru S; Dept. of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Ozorowski G; Dept. of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Turner HL; Dept. of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Antanasijevic A; Dept. of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Huang D; Dept. of Immunology and Microbiology, The Scripps Research Institute, La Jolla CA, 92037, USA.
  • Wang X; Dept. of Molecular Medicine, The Scripps Research Institute, La Jolla CA, 92037, USA.
  • Torres JL; Dept. of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
  • Diedrich JK; Dept. of Molecular Medicine, The Scripps Research Institute, La Jolla CA, 92037, USA.
  • Tian JH; Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD, 20878, USA.
  • Portnoff AD; Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD, 20878, USA.
  • Patel N; Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD, 20878, USA.
  • Massare MJ; Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD, 20878, USA.
  • Yates JR; Dept. of Molecular Medicine, The Scripps Research Institute, La Jolla CA, 92037, USA.
  • Nemazee D; Dept. of Immunology and Microbiology, The Scripps Research Institute, La Jolla CA, 92037, USA.
  • Paulson JC; Dept. of Immunology and Microbiology, The Scripps Research Institute, La Jolla CA, 92037, USA.
  • Glenn G; Dept. of Molecular Medicine, The Scripps Research Institute, La Jolla CA, 92037, USA.
  • Smith G; Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD, 20878, USA.
  • Ward AB; Novavax, Inc. 21 Firstfield Road, Gaithersburg, MD, 20878, USA.
bioRxiv ; 2020 Aug 06.
Article in English | MEDLINE | ID: covidwho-721081
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ABSTRACT
Vaccine efforts against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the current COVID-19 pandemic are focused on SARS-CoV-2 spike glycoprotein, the primary target for neutralizing antibodies. Here, we performed cryo-EM and site-specific glycan analysis of one of the leading subunit vaccine candidates from Novavax based on a full-length spike protein formulated in polysorbate 80 (PS 80) detergent. Our studies reveal a stable prefusion conformation of the spike immunogen with slight differences in the S1 subunit compared to published spike ectodomain structures. Interestingly, we also observed novel interactions between the spike trimers allowing formation of higher order spike complexes. This study confirms the structural integrity of the full-length spike protein immunogen and provides a basis for interpreting immune responses to this multivalent nanoparticle immunogen.
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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines Language: English Year: 2020 Document Type: Article Affiliation country: 2020.08.06.234674

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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines Language: English Year: 2020 Document Type: Article Affiliation country: 2020.08.06.234674