Development of a vaccine against the newly emerging COVID-19 virus based on the receptor binding domain displayed on virus-like particles

Abstract

The recently ermerging disease COVID-19 is caused by the new SARS-CoV-2 virus first detected in the city of Wuhan, China. From there it has been rapidly spreading inside and outside China. With initial death rates around 4%, COVID-19 patients at longer distances from Wuhan showed reduced mortality as was previously observed for the SARS coronavirus. However, the new coronavirus spreads more strongly, as it sheds long before onset of symptoms or may be transmitted by people without symptoms. Rapid development of a protective vaccine against COVID-19 is therefore of paramount importance. Here we demonstrate that recombinantly expressed receptor binding domain (RBD) of the spike protein homologous to SARS binds to ACE2, the viral receptor. Higly repetitive display of RBD on immunologically optimized virus-like particles derived from cucumber mosaic virus resulted in a vaccine candidate (RBD-CuMVTT) that induced high levels of specific antibodies in mice which were able to block binding of spike protein to ACE2 and potently neutralized the SARS-CoV-2 virus in vitro.

Pre-clinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection

“…The optimum sequence and structure of the S protein to be included in a SARS-CoV-2 vaccine is a subject of debate. Several labs have suggested that reducing the S protein to the key neutralizing domains within the receptor binding domain (RBD) would promote higher neutralizing antibody responses, and fewer non-neutralizing antibodies 41,42 . We made a vaccine candidate composed of the S1 domain, which includes the RBD, in an attempt to promote this approach.…”

Vaccines for COVID-19

“…Other groups at the preclinical stage include Saiba AG, based in Switzerland, who are using a cucumber mosaic virus VLP that is bound to SARS‐CoV‐2 RBD, which induced neutralizing antibody in mice [131].…”

COVID-19: Mechanisms of Vaccination and Immunity

“…Another strategy is to display vaccine antigens on VLPs, which are often highly immunogenic. Zha et al have shown that RBD-VLPs efficiently induced SARS-CoV-2-neutralizing antibodies in mice [60]. Further options are to insert RBD into viral vectors or DNA or RNA.…”