Cell Reports
Volume 42, Issue 3, 28 March 2023, 112266
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Article
Design of a stabilized RBD enables potently neutralizing SARS-CoV-2 single-component nanoparticle vaccines

https://doi.org/10.1016/j.celrep.2023.112266Get rights and content
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open access

Highlights

  • Computational design of enhanced SARS-CoV-2 RBD vaccine immunogen

  • Stabilization and removal of glycan enables single-component RBD nanoparticles

  • Nanoparticles elicit significantly more protective antibodies than native RBD

  • Protective antibody levels in monkeys are comparable to benchmark spike antigen

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.

Keywords

structure-based design
structural vaccinology
immunogen
nanoparticle
glycosylation
stabilized
SPEEDesign

Research topic(s)

CP: Immunology
CP: Microbiology

Data and code availability

  • All NHP data are included in Table S1. All other source data will be provided upon request.

  • This paper does not report original code

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

4

Lead contact