A Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Neutralizing Antibody Responses against SARS-CoV-2 in Mice

Abstract

The development of a safe and effective SARS-CoV-2 vaccine is a public health priority. We designed subunit vaccine candidates using self-assembling ferritin nanoparticles displaying one of two multimerized SARS-CoV-2 spikes: full-length ectodomain (S-Fer) or a C-terminal 70 amino-acid deletion (SΔC-Fer). Ferritin is an attractive nanoparticle platform for production of vaccines, and ferritin-based vaccines have been investigated in humans in two separate clinical trials. We confirmed proper folding and antigenicity of spike on the surface of ferritin by cryo-EM and binding to conformation-specific monoclonal antibodies. After a single immunization of mice with either of the two spike ferritin particles, a lentiviral SARS-CoV-2 pseudovirus assay revealed mean neutralizing antibody titers at least 2-fold greater than those in convalescent plasma from COVID-19 patients. Additionally, a single dose of SΔC-Fer elicited significantly higher neutralizing responses as compared to immunization with the spike receptor binding domain (RBD) monomer or spike ectodomain trimer alone. After a second dose, mice immunized with SΔC-Fer exhibited higher neutralizing titers than all other groups. Taken together, these results demonstrate that multivalent presentation of SARS-CoV-2 spike on ferritin can notably enhance elicitation of neutralizing antibodies, thus constituting a viable strategy for single-dose vaccination against COVID-19.

Broadly neutralizing antibodies to SARS-related viruses can be readily induced in rhesus macaques

“…Consistent with earlier studies (38)(39)(40), SARS-CoV-2 S protein immunization of mice elicited high titers of autologous SARS-CoV-2 nAbs; however, the SARS-CoV-1 cross-neutralizing antibody titers were significantly less than the macaque cross-nAb responses (Fig. 1E, fig.…”

COVID-19 Vaccines: Current Understanding on Immunogenicity, Safety, and Further Considerations

“…The types of antigens expressed for the vaccines include RBD-monomer, RBDdimer, RBD-trimer, S1 protein, S protein and S-trimer. Vaccine adjuvants like Al(OH)3, AS01/AS03, Quil-A, monophosphoryl lipid A(MPL), Freund's complete adjuvant, CpG, and Matrix M, Advax ™ , AgnHB have been tested (3,(40)(41)(42)(43)(44)(45)). Novavax's NVX-Cov2373 leads ahead among protein subunit vaccines.…”

Transgene Delivery to Human Induced Pluripotent Stem Cells Using Nanoparticles

“…With advances in nanotechnology and nanoparticle production techniques, the availability and flexibility of nanoparticle platforms have significantly increased. Lipid-based nanoparticles have been employed in the novel mRNA vaccines as those recently made against the SARS-Cov2 coronavirus [21][22][23][24][25][26][27]. These vaccines employ lipid-based nanoparticle capsules which carry the mRNA for coding the spike protein of the virus.…”

“…Increasingly, nanoparticles have been used in biological research and medicine as powerful tools for transgene and drug delivery, imaging, diagnostics, and therapeutics [19,20]. A very successful application of nanoparticles in biomedicine is the extreme fast-pace development of SARS-CoV-2 vaccines, which has saved lives and has helped people to resist the challenges of the COVID-19 pandemic [21][22][23][24][25][26][27]. Nanoparticle-mediated transgene delivery method integrates the strategies and advantages of both the chemical and physical methods, demonstrating the promising and huge application potential.…”