Abstract
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.
Highlights
The rapid development of a SARS-CoV-2 vaccine is a global priority
Covalent coupling of the receptor-binding domain (RBD) antigens to the capsid-like particle (CLP) was confirmed by SDS-PAGE analysis, by the appearance of a protein band of 60 kDa, corresponding to the added size of the RBD antigen (43 kDa) and Tag-CLP subunit (16.5 kDa) (Fig. 1b, lane 2 and 5)
The Tag/Catcher mediated conjugation results in unidirectional display of the RBD antigens, the positioning of the Catcher on the RBD could affect how the antigen is oriented on the CLP surface (Fig. 1c)
Summary
We develop two capsid-like particle (CLP)-based vaccines displaying the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. The spike protein is a primary target for SARS-CoV-2 vaccine development, with emphasis on the receptor-binding domain (RBD), which appears to be the target for most neutralizing antibodies[7,8,9,10,11,12]. The urgent need of an effective SARS-CoV-2 vaccine, to contain the worldwide pandemic and prevent new viral outbreaks, has led to a global effort involving a wide range of vaccine technologies These include genetic-based (mRNA and DNA) principles[13,14], replicating/non-replicating viral vectors (measles[15], adenovirus[16,17], baculovirus), recombinant proteins or peptides[18], virus-like particles (VLPs)/nanoparticles or inactivated and live-attenuated viral vaccines[19,20,21]. CLPs are supramolecular structures assembled from multiple copies of a single viral coat protein, resembling the structure of the virus from which they are derived[28]
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