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Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques
Hannah A. D. King; M. Gordon Joyce; Ines Elakhal Naouar; Aslaa Ahmed; Camila Macedo Cincotta; Caroline Subra; Kristina K. Peachman; Holly H. Hack; Rita E. Chen; Paul V. Thomas; Wei-Hung Chen; Rajeshwer S. Sankhala; Agnes Hajduczki; Elizabeth J. Martinez; Caroline E. Peterson; William C. Chang; Misook Choe; Clayton Smith; Jarrett A. Headley; Hanne A. Elyard; Anthony Cook; Alexander Anderson; Kathryn M. Wuertz; Ming Dong; Isabella Swafford; James B. Case; Jeffrey R. Currier; Kerri G. Lal; Mihret F. Amare; Vincent Dussupt; Sebastian Molnar; Sharon P. Daye; Xiankun Zeng; Erica K. Barkei; Kendra Alfson; Hilary M. Staples; Ricardo Carrion; Shelly J. Krebs; Dominic Paquin-Proulx; Nicos Karasavvas; Victoria R. Polonis; Linda L. Jagodzinski; Sandhya Vasan; Paul T. Scott; Yaoxing Huang; Manoj S. Nair; David D. Ho; Natalia de Val; Michael S. Diamond; Mark G. Lewis; Mangala Rao; Gary R. Matyas; Gregory D. Gromowski; Sheila A. Peel; Nelson L. Michael; Kayvon Modjarrad; Diane L. Bolton.
Affiliation
  • Hannah A. D. King; aUS Military HIV Research Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA. bEmerging Infectious Diseases Branch, WRAIR, Sil
  • M. Gordon Joyce; bEmerging Infectious Diseases Branch, WRAIR, Silver Spring MD 20910, USA. cHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20
  • Ines Elakhal Naouar; cHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA. dDiagnostics and Countermeasures Branch, WRAIR, Silver Spring M
  • Aslaa Ahmed; eViral Diseases Branch, WRAIR, Silver Spring MD 20910, USA.
  • Camila Macedo Cincotta; cHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA. dDiagnostics and Countermeasures Branch, WRAIR, Silver Spring MD
  • Caroline Subra; aUS Military HIV Research Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA. bEmerging Infectious Diseases Branch, WRAIR, Sil
  • Kristina K. Peachman; dDiagnostics and Countermeasures Branch, WRAIR, Silver Spring MD 20910, USA.
  • Holly H. Hack; cHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA. dDiagnostics and Countermeasures Branch, WRAIR, Silver Spring MD
  • Rita E. Chen; fDepartment of Medicine, Washington University, St. Louis, MO 63130, USA. gDepartment of Pathology & Immunology, Washington University, St. Louis, MO 63130, USA
  • Paul V. Thomas; bEmerging Infectious Diseases Branch, WRAIR, Silver Spring MD 20910, USA. cHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20
  • Wei-Hung Chen; bEmerging Infectious Diseases Branch, WRAIR, Silver Spring MD 20910, USA. cHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20
  • Rajeshwer S. Sankhala; bEmerging Infectious Diseases Branch, WRAIR, Silver Spring MD 20910, USA. cHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20
  • Agnes Hajduczki; bEmerging Infectious Diseases Branch, WRAIR, Silver Spring MD 20910, USA. cHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20
  • Elizabeth J. Martinez; bEmerging Infectious Diseases Branch, WRAIR, Silver Spring MD 20910, USA. cHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20
  • Caroline E. Peterson; bEmerging Infectious Diseases Branch, WRAIR, Silver Spring MD 20910, USA. cHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20
  • William C. Chang; bEmerging Infectious Diseases Branch, WRAIR, Silver Spring MD 20910, USA. cHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20
  • Misook Choe; bEmerging Infectious Diseases Branch, WRAIR, Silver Spring MD 20910, USA. cHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20
  • Clayton Smith; hCenter for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
  • Jarrett A. Headley; bEmerging Infectious Diseases Branch, WRAIR, Silver Spring MD 20910, USA. cHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20
  • Hanne A. Elyard; iBIOQUAL, Inc., Rockville, MD 20850, USA.
  • Anthony Cook; iBIOQUAL, Inc., Rockville, MD 20850, USA.
  • Alexander Anderson; aUS Military HIV Research Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA. bEmerging Infectious Diseases Branch, WRAIR, Si
  • Kathryn M. Wuertz; aUS Military HIV Research Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA.
  • Ming Dong; aUS Military HIV Research Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA. bEmerging Infectious Diseases Branch, WRAIR, Si
  • Isabella Swafford; aUS Military HIV Research Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA. bEmerging Infectious Diseases Branch, WRAIR, Si
  • James B. Case; fDepartment of Medicine, Washington University, St. Louis, MO 63130, USA.
  • Jeffrey R. Currier; eViral Diseases Branch, WRAIR, Silver Spring MD 20910, USA.
  • Kerri G. Lal; aUS Military HIV Research Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA. bEmerging Infectious Diseases Branch, WRAIR, Si
  • Mihret F. Amare; bEmerging Infectious Diseases Branch, WRAIR, Silver Spring MD 20910, USA. cHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20
  • Vincent Dussupt; aUS Military HIV Research Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA. bEmerging Infectious Diseases Branch, WRAIR, Si
  • Sebastian Molnar; aUS Military HIV Research Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA. bEmerging Infectious Diseases Branch, WRAIR, Si
  • Sharon P. Daye; jCenter for Infectious Diseases Research, WRAIR, Silver Spring MD 20910, USA.
  • Xiankun Zeng; kDivision of Pathology, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
  • Erica K. Barkei; lVeterinary Pathology Branch, WRAIR, Silver Spring MD 20910, USA.
  • Kendra Alfson; mDisease Intervention and Prevention, Texas Biomedical Research Institute, San Antonio TX 78227, USA.
  • Hilary M. Staples; mDisease Intervention and Prevention, Texas Biomedical Research Institute, San Antonio TX 78227, USA.
  • Ricardo Carrion; mDisease Intervention and Prevention, Texas Biomedical Research Institute, San Antonio TX 78227, USA.
  • Shelly J. Krebs; aUS Military HIV Research Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA. bEmerging Infectious Diseases Branch, WRAIR, Si
  • Dominic Paquin-Proulx; aUS Military HIV Research Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA. bEmerging Infectious Diseases Branch, WRAIR, Si
  • Nicos Karasavvas; cHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda MD 20817, USA. dDiagnostics and Countermeasures Branch, WRAIR, Silver Spring M
  • Victoria R. Polonis; aUS Military HIV Research Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA.
  • Linda L. Jagodzinski; dDiagnostics and Countermeasures Branch, WRAIR, Silver Spring MD 20910, USA.
  • Sandhya Vasan; aUS Military HIV Research Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA. bEmerging Infectious Diseases Branch, WRAIR, Si
  • Paul T. Scott; bEmerging Infectious Diseases Branch, WRAIR, Silver Spring MD 20910, USA.
  • Yaoxing Huang; nAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
  • Manoj S. Nair; nAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
  • David D. Ho; nAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
  • Natalia de Val; hCenter for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
  • Michael S. Diamond; fDepartment of Medicine, Washington University, St. Louis, MO 63130, USA. gDepartment of Pathology & Immunology, Washington University, St. Louis, MO 63130, USA
  • Mark G. Lewis; iBIOQUAL, Inc., Rockville, MD 20850, USA.
  • Mangala Rao; aUS Military HIV Research Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA.
  • Gary R. Matyas; aUS Military HIV Research Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA.
  • Gregory D. Gromowski; eViral Diseases Branch, WRAIR, Silver Spring MD 20910, USA.
  • Sheila A. Peel; dDiagnostics and Countermeasures Branch, WRAIR, Silver Spring MD 20910, USA.
  • Nelson L. Michael; jCenter for Infectious Diseases Research, WRAIR, Silver Spring MD 20910, USA.
  • Kayvon Modjarrad; bEmerging Infectious Diseases Branch, WRAIR, Silver Spring MD 20910, USA.
  • Diane L. Bolton; aUS Military HIV Research Program, Walter Reed Army Institute of Research (WRAIR), Silver Spring MD 20910, USA. bEmerging Infectious Diseases Branch, WRAIR, Si
Preprint in En | PREPRINT-BIORXIV | ID: ppbiorxiv-439166
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ABSTRACT
Emergence of novel variants of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean neutralizing antibody titers of 14,000-21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within four days in 7 of 8 animals receiving 50 {micro}g RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only [~]2-fold relative to USA-WA1. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-like betacoronavirus vaccine development. Significance StatementThe emergence of SARS-CoV-2 variants of concern (VOC) that reduce the efficacy of current COVID-19 vaccines is a major threat to pandemic control. We evaluate a SARS-CoV-2 Spike receptor-binding domain ferritin nanoparticle protein vaccine (RFN) in a nonhuman primate challenge model that addresses the need for a next-generation, efficacious vaccine with increased pan-SARS breadth of coverage. RFN, adjuvanted with a liposomal-QS21 formulation (ALFQ), elicits humoral and cellular immune responses exceeding those of current vaccines in terms of breadth and potency and protects against high-dose respiratory tract challenge. Neutralization activity against the B.1.351 VOC within two-fold of wild-type virus and against SARS-CoV-1 indicate exceptional breadth. Our results support consideration of RFN for SARS-like betacoronavirus vaccine development.
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Full text: 1 Collection: 09-preprints Database: PREPRINT-BIORXIV Type of study: Experimental_studies / Rct Language: En Year: 2021 Document type: Preprint
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Full text: 1 Collection: 09-preprints Database: PREPRINT-BIORXIV Type of study: Experimental_studies / Rct Language: En Year: 2021 Document type: Preprint