SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity.

Journal

bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
10 May 2021
Historique:
entrez: 20 5 2021
pubmed: 21 5 2021
medline: 21 5 2021
Statut: epublish

Résumé

The need for SARS-CoV-2 next-generation vaccines has been highlighted by the rise of variants of concern (VoC) and the long-term threat of other coronaviruses. Here, we designed and characterized four categories of engineered nanoparticle immunogens that recapitulate the structural and antigenic properties of prefusion Spike (S), S1 and RBD. These immunogens induced robust S-binding, ACE2-inhibition, and authentic and pseudovirus neutralizing antibodies against SARS-CoV-2 in mice. A Spike-ferritin nanoparticle (SpFN) vaccine elicited neutralizing titers more than 20-fold higher than convalescent donor serum, following a single immunization, while RBD-Ferritin nanoparticle (RFN) immunogens elicited similar responses after two immunizations. Passive transfer of IgG purified from SpFN- or RFN-immunized mice protected K18-hACE2 transgenic mice from a lethal SARS-CoV-2 virus challenge. Furthermore, SpFN- and RFN-immunization elicited ACE2 blocking activity and neutralizing ID50 antibody titers >2,000 against SARS-CoV-1, along with high magnitude neutralizing titers against major VoC. These results provide design strategies for pan-coronavirus vaccine development. Iterative structure-based design of four Spike-domain Ferritin nanoparticle classes of immunogensSpFN-ALFQ and RFN-ALFQ immunization elicits potent neutralizing activity against SARS-CoV-2, variants of concern, and SARS-CoV-1Passively transferred IgG from immunized C57BL/6 mice protects K18-hACE2 mice from lethal SARS-CoV-2 challenge.

Identifiants

DOI: 10.1101/2021.05.09.443331 PMID: 34013273 PMC: PMC8132231
pubmed: 34013273
doi: 10.1101/2021.05.09.443331
pmc: PMC8132231
pii:
doi:

Types de publication

Preprint

Langues

eng

Commentaires et corrections

Type : UpdateIn

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Auteurs

M Gordon Joyce (MG)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
Lead contact.

Wei-Hung Chen (WH)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Rajeshwer S Sankhala (RS)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Agnes Hajduczki (A)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Paul V Thomas (PV)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Misook Choe (M)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

William Chang (W)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Caroline E Peterson (CE)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Elizabeth Martinez (E)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Elaine B Morrison (EB)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Clayton Smith (C)

Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD, USA.

Aslaa Ahmed (A)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Lindsay Wieczorek (L)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Alexander Anderson (A)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Rita E Chen (RE)

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA.

James Brett Case (JB)

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA.

Yifan Li (Y)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Therese Oertel (T)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Lorean Rosado (L)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Akshaya Ganesh (A)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Connor Whalen (C)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Joshua M Carmen (JM)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Letzibeth Mendez-Rivera (L)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Christopher Karch (C)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Neelakshi Gohain (N)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Zuzana Villar (Z)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

David McCurdy (D)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Zoltan Beck (Z)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Jiae Kim (J)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Shikha Shrivastava (S)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Ousman Jobe (O)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Vincent Dussupt (V)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Sebastian Molnar (S)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Ursula Tran (U)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Chandrika B Kannadka (CB)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Michelle Zemil (M)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Htet Khanh (H)

Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD, USA.

Weimin Wu (W)

Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD, USA.

Matthew A Cole (MA)

Trudeau Institute, Inc., Saranac Lake, NY, USA.

Debra K Duso (DK)

Trudeau Institute, Inc., Saranac Lake, NY, USA.

Larry W Kummer (LW)

Trudeau Institute, Inc., Saranac Lake, NY, USA.

Tricia J Lang (TJ)

Trudeau Institute, Inc., Saranac Lake, NY, USA.

Shania E Muncil (SE)

Trudeau Institute, Inc., Saranac Lake, NY, USA.

Jeffrey R Currier (JR)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Shelly J Krebs (SJ)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Victoria R Polonis (VR)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Saravanan Rajan (S)

Antibody Discovery and Protein Engineering (ADPE), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, USA.

Patrick M McTamney (PM)

Microbial Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.

Mark T Esser (MT)

Microbial Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.

William W Reiley (WW)

Trudeau Institute, Inc., Saranac Lake, NY, USA.

Morgane Rolland (M)

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Natalia de Val (N)

Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD, USA.

Michael S Diamond (MS)

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA.

Gregory D Gromowski (GD)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Gary R Matyas (GR)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Mangala Rao (M)

U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Nelson L Michael (NL)

Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Kayvon Modjarrad (K)

Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Classifications MeSH