Design of a stabilized RBD enables potently neutralizing SARS-CoV-2 single-component nanoparticle vaccines

Thayne H. Dickey; Rui Ma; Sachy Orr-Gonzalez; Tarik Ouahes; Palak Patel; Holly McAleese; Brandi Butler; Elizabeth Eudy; Brett Eaton; Michael Murphy; Jennifer L. Kwan; Nichole D. Salinas; Michael R. Holbrook; Lynn E. Lambert; Niraj H. Tolia

Cell Reports (Mar 2023)

Design of a stabilized RBD enables potently neutralizing SARS-CoV-2 single-component nanoparticle vaccines

Thayne H. Dickey,
Rui Ma,
Sachy Orr-Gonzalez,
Tarik Ouahes,
Palak Patel,
Holly McAleese,
Brandi Butler,
Elizabeth Eudy,
Brett Eaton,
Michael Murphy,
Jennifer L. Kwan,
Nichole D. Salinas,
Michael R. Holbrook,
Lynn E. Lambert,
Niraj H. Tolia

Affiliations

Thayne H. Dickey: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20894, USA
Rui Ma: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20894, USA
Sachy Orr-Gonzalez: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20894, USA
Tarik Ouahes: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20894, USA
Palak Patel: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20894, USA
Holly McAleese: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20894, USA
Brandi Butler: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20894, USA
Elizabeth Eudy: Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Frederick, MD 21702, USA
Brett Eaton: Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Frederick, MD 21702, USA
Michael Murphy: Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Frederick, MD 21702, USA
Jennifer L. Kwan: Epidemiology and Population Studies Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20894, USA
Nichole D. Salinas: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20894, USA
Michael R. Holbrook: Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Frederick, MD 21702, USA
Lynn E. Lambert: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20894, USA
Niraj H. Tolia: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20894, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 3
p. 112266

Abstract

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Summary: Waning immunity and emerging variants necessitate continued vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Improvements in vaccine safety, tolerability, and ease of manufacturing would benefit these efforts. Here, we develop a potent and easily manufactured nanoparticle vaccine displaying the spike receptor-binding domain (RBD). Computational design to stabilize the RBD, eliminate glycosylation, and focus the immune response to neutralizing epitopes results in an RBD immunogen that resolves issues hindering the efficient nanoparticle display of the native RBD. This non-glycosylated RBD can be genetically fused to diverse single-component nanoparticle platforms, maximizing manufacturing ease and flexibility. All engineered RBD nanoparticles elicit potently neutralizing antibodies in mice that far exceed monomeric RBDs. A 60-copy particle (noNAG-RBD-E2p) also elicits potently neutralizing antibodies in non-human primates. The neutralizing antibody titers elicited by noNAG-RBD-E2p are comparable to a benchmark stabilized spike antigen and reach levels against Omicron BA.5 that suggest that it would provide protection against emerging variants.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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