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SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice
Jing-Hui Tian; Nita Patel; Robert Haupt; Haixia Zhou; Stuart Weston; Holly Hammond; James Lague; Alyse D Portnoff; James Norton; Mimi Guebre-Xabier; Bin Zhou; Kelsey Jacobson; Sonai Maciejewski; Rafia Khatoon; Malgorzata Wisniewska; Will Mottitt; Stenfanie Kluepfel-Stahl; Betty Ekechukwu; James Papin; Sarathi Boddapati; C. Jason Wong; Pedro A Piedra; Matthew B Frieman; Michael J Massare; Louis Fries; Karin Lovgren Bengtsson; Linda Stertman; Larry R Ellingsworth; Gregory Glenn; Gale Smith.
Afiliación
  • Jing-Hui Tian; Novavax, Inc.
  • Nita Patel; Novavax, Inc.
  • Robert Haupt; University of Maryland, School of Medicine
  • Haixia Zhou; Novavax, Inc.
  • Stuart Weston; University of Maryland, School of Medicine
  • Holly Hammond; University of Maryland, School of Medicine
  • James Lague; University of Maryland, School of Medicine
  • Alyse D Portnoff; Novavax, Inc.
  • James Norton; Novavax, Inc.
  • Mimi Guebre-Xabier; Novavax, Inc.
  • Bin Zhou; Novavax, Inc.
  • Kelsey Jacobson; Novavax, Inc.
  • Sonai Maciejewski; Novavax, Inc.
  • Rafia Khatoon; Novavax, Inc.
  • Malgorzata Wisniewska; Novavax, Inc.
  • Will Mottitt; Novavax, Inc.
  • Stenfanie Kluepfel-Stahl; Novavax, Inc.
  • Betty Ekechukwu; Novavax, Inc.
  • James Papin; University of Oklahoma, Health Sciences Center, Department of Pathology, Division of Comparative Medicine
  • Sarathi Boddapati; Catalent Paragon Gene Therapy
  • C. Jason Wong; Catalent Paragon Gene Therapy
  • Pedro A Piedra; Department of Molecular Virology and Microbiology, and Pediatrics, Baylor College of Medicine
  • Matthew B Frieman; University of Maryland, School of Medicine
  • Michael J Massare; Novavax, Inc.
  • Louis Fries; Novavax, Inc.
  • Karin Lovgren Bengtsson; Novavax, AB
  • Linda Stertman; Novavax, AB
  • Larry R Ellingsworth; Novavax, Inc.
  • Gregory Glenn; Novavax, Inc.
  • Gale Smith; Novavax, Inc.
Preprint en En | PREPRINT-BIORXIV | ID: ppbiorxiv-178509
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ABSTRACT
The COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd immunity to control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length spike (S) protein, stabilized in the prefusion conformation. Purified NVX-CoV2373 S form 27.2nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice and baboons, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicits high titer anti-S IgG that is associated with blockade of hACE2 receptor binding, virus neutralization, and protection against SARS-CoV-2 challenge in mice with no evidence of vaccine-associated enhanced respiratory disease (VAERD). NVX-CoV2373 vaccine also elicits multifunctional CD4+ and CD8+ T cells, CD4+ T follicular helper T cells (Tfh), and the generation of antigen-specific germinal center (GC) B cells in the spleen. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2327 with Matrix-M (NCT04368988).
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Experimental_studies / Prognostic_studies Idioma: En Año: 2020 Tipo del documento: Preprint
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Experimental_studies / Prognostic_studies Idioma: En Año: 2020 Tipo del documento: Preprint