Rapid development of SARS-CoV-2 receptor binding domain-conjugated nanoparticle vaccine candidate

Abstract

The ongoing of coronavirus disease 2019 (COVID-19) pandemic caused by novel SARS-CoV-2 coronavirus, resulting in economic losses and seriously threating the human health in worldwide, highlighting the urgent need of a stabilized, easily produced and effective preventive vaccine. The SARS-COV-2 spike protein receptor binding region (RBD) plays an important role in the process of viral binding receptor angiotensin-converting enzyme 2 (ACE2) and membrane fusion, making it an ideal target for vaccine development. In this study, we designed three different RBD-conjugated nanoparticles vaccine candidates, RBD-Ferritin (24-mer), RBD-mi3 (60-mer) and RBD-I53-50 (120-mer), with the application of covalent bond linking by SpyTag-SpyCatcher system. It was demonstrated that the neutralizing capability of sera from mice immunized with three RBD-conjugated nanoparticles adjuvanted with AddaVax or Sigma Systerm Adjuvant (SAS) after each immunization was ~8- to 120-fold greater than monomeric RBD group in SARS-CoV-2 pseudovirus and authentic virus neutralization assay. Most importantly, sera from RBD-conjugated NPs groups more efficiently blocked the binding of RBD to ACE2 or neutralizing antibody in vitro, a further proof of promising immunization effect. Besides, high physical stability and flexibility in assembly consolidated the benefit for rapid scale-up production of vaccine. These results supported that our designed SARS-CoV-2 RBD-conjugated nanoparticle was competitive vaccine candidate and the carrier nanoparticles could be adopted as universal platform for future vaccine development.

State-of-the-Art of Nanodiagnostics and Nanotherapeutics against SARS-CoV-2

“…In a similar study, RBD-conjugated ferritin nanoparticles were prepared using a SpyTag/SpyCatcher strategy. 195 All findings support the idea of utilizing self-assembled ferritin NPs as an efficient carrier for SARS-CoV-2 antigens toward vaccine development.…”

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.…”

Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques

“…Presenting RBD in ordered, multivalent arrays on the surface of self-assembling protein nanoparticles is immunogenic and efficacious in animals (23)(24)(25)(26)(27)(28), with improved immunogenicity relative to monomeric soluble RBD and cross-reactive responses to variants (17,24,26). However, it is unknown whether RBD nanoparticle vaccines are able to protect against infection in primates, which have become a standard model for benchmarking performance of vaccine candidates.…”