Working Paper Brief Report Version 2 This version is not peer-reviewed

Potential for Developing a SARS-CoV Receptor Binding Domain (RBD) Recombinant Protein as a Heterologous Human Vaccine against Coronavirus Infectious Disease (COVID)-19

Version 1 : Received: 25 February 2020 / Approved: 29 February 2020 / Online: 29 February 2020 (03:20:37 CET)
Version 2 : Received: 2 March 2020 / Approved: 4 March 2020 / Online: 4 March 2020 (05:19:16 CET)

A peer-reviewed article of this Preprint also exists.


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 minimal 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 against Coronavirus Infectious Disease (COVID)-19. 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 against COVID-19, 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 region (59%). However, the high similarity (94%) in the region outside of RBM offers the potential of conserved neutralizing epitopes between both viruses.


heterologous vaccine; receptor-binding domain; subunit vaccine; coronavirus; COVID-19; SARS; SARS-CoV-2


Medicine and Pharmacology, Pulmonary and Respiratory Medicine

Comments (1)

Comment 1
Received: 4 March 2020
Commenter: Wen-Hsiang Chen
Commenter's Conflict of Interests: Author
Comment: Changed 'it's' to 'it has' in Line 64 and to 'its' in Line 98.
Change 'mabs' to 'mAbs' to be consistent with Table 1 and with mAbs as used in the field in general.
Changed "do not only recognize epitopes' to 'recognize epitopes other than"
Lines 16 and 45, changed low immunopathlogy to minimal immunopathlogy.
In the conclusion section, we have added the next steps for parallel activities to develop a homologous antigen.
Minor updated on the figure.
Made minor updates on the title and abstract after the above updates.
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