Immune response to vaccine candidates based on different types of nanoscaffolded RBD domain of the SARS-CoV-2 spike protein

Abstract

Effective and safe vaccines against SARS-CoV-2 are highly desirable to prevent casualties and societal cost caused by Covid-19 pandemic. The receptor binding domain (RBD) of the surface-exposed spike protein of SARS-CoV-2 represents a suitable target for the induction of neutralizing antibodies upon vaccination. Small protein antigens typically induce weak immune response while particles measuring tens of nanometers are efficiently presented to B cell follicles and subsequently to follicular germinal center B cells in draining lymph nodes, where B cell proliferation and affinity maturation occurs. Here we prepared and analyzed the response to several DNA vaccines based on genetic fusions of RBD to four different scaffolding domains, namely to the foldon peptide, ferritin, lumazine synthase and β-annulus peptide, presenting from 6 to 60 copies of the RBD on each particle. Scaffolding strongly augmented the immune response with production of neutralizing antibodies and T cell response including cytotoxic lymphocytes in mice upon immunization with DNA plasmids. The most potent response was observed for the 24-residue β-annulus peptide scaffold that forms large soluble assemblies, that has the advantage of low immunogenicity in comparison to larger scaffolds. Our results support the advancement of this vaccine platform towards clinical trials.

A Nanoscaffolded Spike-RBD Vaccine Provides Protection against SARS-CoV-2 with Minimal Anti-Scaffold Response

“…Immunization with AaLs- and ferritin-scaffolded RBD, in contrast, generated a strong response against the scaffold. A strong immune response against RBD-ferritin has been confirmed in a recent paper [ 55 ] submitted after the version of this report had been deposited to the bioRxiv [ 60 ]. This scaffold-targeted response could be deleterious for repeated immunizations, similarly to adenoviral vaccines [ 61 ].…”

Mechanism of a COVID-19 nanoparticle vaccine candidate that elicits a broadly neutralizing antibody response to SARS-CoV-2 variants

“…Superior NAb responses have been reported for other COVID-19 vaccine candidates that take advantage of particulate display (66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78). Importantly, our S2GΔHR2-presenting I3-01v9 SApNP vaccine elicited bNAb responses to three SARS-CoV-2 VOCs (Fig.…”

Protein-based antigen presentation platforms for nanoparticle vaccines

“…A conclusive answer to the impact of valency will require testing of valencies with optimally spaced antigen. Antibody responses against the platform has been demonstrated in vaccines 97 , which may potentially divert the humoral immune response from the antigen. Continued research and testing of more platforms are needed to determine the effects of this implication, as well as evaluate parameters for the development of more optimized platforms.…”