Capsid-like Particles Decorated with the SARS-CoV-2 Receptor-binding Domain Elicit Strong Virus Neutralization Activity

The rapid development of a SARS-CoV-2 vaccine is a global priority. Here, we develop two capsid-like particle (CLP)-based vaccines displaying the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. RBD antigens are displayed on AP205 CLPs through a split-protein Tag/Catcher, ensuring unidirectional and high-density display of RBD. Both soluble recombinant RBD and RBD displayed on CLPs bind the ACE2 receptor with nanomolar affinity. Mice are vaccinated with soluble RBD or CLP-displayed RBD, formulated in Squalene-Water-Emulsion. The RBD-CLP vaccines induce higher levels of serum anti-spike antibodies than the soluble RBD vaccines. Remarkably, one injection with our lead RBD-CLP vaccine in mice elicits virus neutralization antibody titers comparable to those found in patients that had recovered from COVID-19. Following booster vaccinations, the virus neutralization titers exceed those measured after natural infection, at serum dilutions above 1:10,000. Thus, the RBD-CLP vaccine is a highly promising candidate for preventing COVID-19.

Citing Articles

A self-adjuvanted VLPs-based Covid-19 vaccine proven versatile, safe, and highly protective.

Vuitika L, Cortes N, Malaquias V, Silva J, Lira A, Prates-Syed W Sci Rep. 2024; 14(1):24228.

PMID: 39414952 PMC: 11484777. DOI: 10.1038/s41598-024-76163-w.

Broadly potent spike-specific human monoclonal antibodies inhibit SARS-CoV-2 Omicron sub-lineages.

Walker M, Underwood A, Bjornsson K, Raghavan S, Bassi M, Binderup A Commun Biol. 2024; 7(1):1239.

PMID: 39354108 PMC: 11445456. DOI: 10.1038/s42003-024-06951-7.

Molecular Design of Encapsulin Protein Nanoparticles to Display Rotavirus Antigens for Enhancing Immunogenicity.

Jung H, Jeong S, Kang M, Hong I, Park Y, Ko E Vaccines (Basel). 2024; 12(9).

PMID: 39340050 PMC: 11435836. DOI: 10.3390/vaccines12091020.

Leveraging Immunofocusing and Virus-like Particle Display to Enhance Antibody Responses to the Malaria Blood-Stage Invasion Complex Antigen PfCyRPA.

Bjornsson K, Bassi M, Knudsen A, Aves K, Morella Roig E, Sander A Vaccines (Basel). 2024; 12(8).

PMID: 39203985 PMC: 11359962. DOI: 10.3390/vaccines12080859.

Genetic Functionalization of Protein-Based Biomaterials via Protein Fusions.

Mendes G, Faulk B, Kaparthi B, Irion A, Fong B, Bayless K Biomacromolecules. 2024; 25(8):4639-4662.

PMID: 39074364 PMC: 11323028. DOI: 10.1021/acs.biomac.4c00188.

References

Keeble A, Turkki P, Stokes S, Khairil Anuar I, Rahikainen R, Hytonen V . Approaching infinite affinity through engineering of peptide-protein interaction. Proc Natl Acad Sci U S A. 2019; 116(52):26523-26533. PMC: 6936558. DOI: 10.1073/pnas.1909653116. View

Brune K, Leneghan D, Brian I, Ishizuka A, Bachmann M, Draper S . Plug-and-Display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization. Sci Rep. 2016; 6:19234. PMC: 4725971. DOI: 10.1038/srep19234. View

Li L, Fierer J, Rapoport T, Howarth M . Structural analysis and optimization of the covalent association between SpyCatcher and a peptide Tag. J Mol Biol. 2013; 426(2):309-17. PMC: 3959856. DOI: 10.1016/j.jmb.2013.10.021. View

Thrane S, Janitzek C, Matondo S, Resende M, Gustavsson T, Adriaan de Jongh W . Bacterial superglue enables easy development of efficient virus-like particle based vaccines. J Nanobiotechnology. 2016; 14:30. PMC: 4847360. DOI: 10.1186/s12951-016-0181-1. View

Chen W, Tao X, Agrawal A, Algaissi A, Peng B, Pollet J . Yeast-expressed SARS-CoV recombinant receptor-binding domain (RBD219-N1) formulated with aluminum hydroxide induces protective immunity and reduces immune enhancement. Vaccine. 2020; 38(47):7533-7541. PMC: 7508514. DOI: 10.1016/j.vaccine.2020.09.061. View

Smith T, Patel A, Ramos S, Elwood D, Zhu X, Yan J . Immunogenicity of a DNA vaccine candidate for COVID-19. Nat Commun. 2020; 11(1):2601. PMC: 7239918. DOI: 10.1038/s41467-020-16505-0. View

Buldun C, Jean J, Bedford M, Howarth M . SnoopLigase Catalyzes Peptide-Peptide Locking and Enables Solid-Phase Conjugate Isolation. J Am Chem Soc. 2018; 140(8):3008-3018. DOI: 10.1021/jacs.7b13237. View

Mohsen M, Gomes A, Vogel M, Bachmann M . Interaction of Viral Capsid-Derived Virus-Like Particles (VLPs) with the Innate Immune System. Vaccines (Basel). 2018; 6(3). PMC: 6161069. DOI: 10.3390/vaccines6030037. View

Simon H, Karaulov A, Bachmann M . Strategies to Prevent SARS-CoV-2-Mediated Eosinophilic Disease in Association with COVID-19 Vaccination and Infection. Int Arch Allergy Immunol. 2020; 181(8):624-628. PMC: 7360494. DOI: 10.1159/000509368. View

10.

Lambert P, Ambrosino D, Andersen S, Baric R, Black S, Chen R . Consensus summary report for CEPI/BC March 12-13, 2020 meeting: Assessment of risk of disease enhancement with COVID-19 vaccines. Vaccine. 2020; 38(31):4783-4791. PMC: 7247514. DOI: 10.1016/j.vaccine.2020.05.064. View

11.

Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S . Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 2020; 581(7807):215-220. DOI: 10.1038/s41586-020-2180-5. View

12.

Lu R, Zhao X, Li J, Niu P, Yang B, Wu H . Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020; 395(10224):565-574. PMC: 7159086. DOI: 10.1016/S0140-6736(20)30251-8. View

13.

Amanna I . Balancing the Efficacy and Safety of Vaccines in the Elderly. Open Longev Sci. 2013; 6(2012):64-72. PMC: 3616444. DOI: 10.2174/1876326X01206010064. View

14.

Kim E, Erdos G, Huang S, Kenniston T, Balmert S, Donahue Carey C . Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development. EBioMedicine. 2020; 55:102743. PMC: 7128973. DOI: 10.1016/j.ebiom.2020.102743. View

15.

Kutzler M, Weiner D . DNA vaccines: ready for prime time?. Nat Rev Genet. 2008; 9(10):776-88. PMC: 4317294. DOI: 10.1038/nrg2432. View

16.

De Vincenzo R, Conte C, Ricci C, Scambia G, Capelli G . Long-term efficacy and safety of human papillomavirus vaccination. Int J Womens Health. 2015; 6:999-1010. PMC: 4262378. DOI: 10.2147/IJWH.S50365. View

17.

Pumpens P, Renhofa R, Dishlers A, Kozlovska T, Ose V, Pushko P . The True Story and Advantages of RNA Phage Capsids as Nanotools. Intervirology. 2016; 59(2):74-110. DOI: 10.1159/000449503. View

18.

Cao Y, Su B, Guo X, Sun W, Deng Y, Bao L . Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells. Cell. 2020; 182(1):73-84.e16. PMC: 7231725. DOI: 10.1016/j.cell.2020.05.025. View

19.

Janitzek C, Matondo S, Thrane S, Nielsen M, Kavishe R, Mwakalinga S . Bacterial superglue generates a full-length circumsporozoite protein virus-like particle vaccine capable of inducing high and durable antibody responses. Malar J. 2016; 15(1):545. PMC: 5101663. DOI: 10.1186/s12936-016-1574-1. View

20.

Schiller J, Lowy D . Explanations for the high potency of HPV prophylactic vaccines. Vaccine. 2018; 36(32 Pt A):4768-4773. PMC: 6035892. DOI: 10.1016/j.vaccine.2017.12.079. View