One dose of COVID-19 nanoparticle vaccine REVC-128 provides protection against SARS-CoV-2 challenge at two weeks post immunization

Abstract

A COVID-19 vaccine with capability to induce early protection is needed to efficiently eliminate viral spread. Here, we demonstrate the development of a nanoparticle vaccine candidate, REVC-128, in which multiple trimeric spike ectodomain subunits with glycine (G) at position 614 were multimerized onto a nanoparticle. In-vitro characterization of this vaccine confirms its structural and antigenic integrity. In-vivo immunogenicity evaluation in mice indicates that a single dose of this vaccine induces potent serum neutralizing antibody titer at two weeks post immunization, which is significantly higher than titer induced by trimeric spike protein without nanoparticle presentation. The comparison of serum binding to spike subunits between animals immunized by spike with and without nanoparticle presentation indicates that nanoparticle prefers the display of spike RBD (Receptor-Binding Domain) over S2 subunit, likely resulting in a more neutralizing but less cross-reactive antibody response. Moreover, a Syrian golden hamster in-vivo model for SARS-CoV-2 virus challenge was implemented at two weeks post a single dose of REVC-128 immunization. The results show that vaccination protects hamsters against SARS-CoV-2 virus challenge with evidence of steady body weight, suppressed viral loads and alleviation of tissue damage (lung and nares) for protected animals, compared with ~10% weight loss, higher viral loads and tissue damage in unprotected animals. Furthermore, the data show that vaccine REVC-128 is thermostable at up to 37°C for at least 4 weeks. These findings, along with a long history of safety for protein vaccines, suggest that the REVC-128 is a safe, stable and efficacious single-shot vaccine candidate to induce the earliest protection against SARS-CoV-2 infection.

Complete protection by a single-dose skin patch–delivered SARS-CoV-2 spike vaccine

“…Without Matrix-M, the same 10-g dose offered little protection even after two doses. Another study used a spike nanoparticle vaccine in which multiple spike proteins are assembled on a nanoparticle (69). Immunization provided protection in hamsters, although this immunity was not complete and required a dose of 100 g, 50 times higher than required by HD-MAP immunization (69).…”

Pre-vaccination and early B cell signatures predict antibody response to SARS-CoV-2 mRNA vaccine

“…A SARS-CoV-2 RBD construct containing a His-tag and Avi-tag was generated, as previously described 30 . The residues 319-541 of the S protein were codon optimized with N-terminal of signal peptide (MFVFLVLLPLVSSQ) and C-terminal of 6-His tag and Avi-tag (GLNDIFEAQKIEWHE).…”

Single‐dose immunisation with a multimerised SARS‐CoV‐2 receptor binding domain (RBD) induces an enhanced and protective response in mice

“…Previous work has shown that protein-based subunit vaccines directed against SARS-CoV-2 deliver high antibody responses in animal models (Tan et al, 2021;Wang et al, 2021). Furthermore, subunit antigens have the potential to deliver a cheaper, boostable and more robust alternative to nucleic-acid based vaccines (Dalvie et al, 2021;Gu et al, 2021;He et al, 2021;Joyce et al, 2021;Kalathiya et al, 2021;Koenig et al, 2021;Ma et al, 2020;Powell et al, 2021;Saunders et al, 2021;Xiang et al, 2020). To explore the development of stable and efficient subunit vaccine candidates, here we covalently linked SARS-CoV-2 proteins expressed in mammalian and bacterial cells with bacterially-expressed Dps from the hyperthermophilic archaeon Sulfolubus islandicus (Gauss et al, 2006).…”