Potential for Developing the SARS-CoV Receptor Binding Domain Recombinant Protein (RBD) as a Heterologous Human Vaccine for SARS-CoV-2

A SARS-CoV receptor-binding domain (RBD) recombinant protein was developed and manufactured under current good manufacturing practices in 2016. The protein known as RBD219-N1 when formulated on Alhydrogel®, induced high-level neutralizing antibodies and protective immunity with low immunopathology in mice after a homologous virus challenge with SARS-CoV (MA15 strain). In this report, we examined published evidence in support of whether the SARS-CoV RBD219-N1 could be repurposed as a heterologous vaccine for SARS-CoV-2. Our findings include evidence that convalescent serum from SARS-CoV patients can neutralize SARS-CoV-2. Additionally, a review of published studies using monoclonal antibodies (mabs) raised against SARS-CoV RBD and that neutralize the SARS-CoV virus in vitro, finds that some of these mabs bind to the receptor-binding motif (RBM) within the RBD, while others bind to domains outside this region within RBD. This information is relevant and supports the possibility of developing a heterologous SARS-CoV RBD vaccine, especially due to the finding that the overall high amino acid similarity (82%) between SARS-CoV and SARS-CoV-2 spike and RBD domains is not reflected in RBM amino acid similarity (59%). However, the high sequence similarity (94%) in the region outside of RBM offers the potential of conserved neutralizing epitopes between both viruses.