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
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.
