The E and M proteins have important functions in the viral assembly of a coronavirus, and the N protein is necessary for viral RNA synthesis13. Deletion of E protein abrogated the virulence of CoVs, and several studies have explored the potential of recombinant SARS-CoV or MERS-CoV with a mutated E protein as live attenuated vaccines13,14. The M protein can augment the immune response induced by N protein DNA vaccine against SARS-CoV;15 however, the conserved N protein across CoV families implies that it is not a suitable candidate for vaccine development, and the antibodies against the N protein of SARS-CoV-2 do not provide immunity to the infection16. The critical glycoprotein S of SARS-CoV-2 is responsible for virus binding and entry16. The S precursor protein of SARS-CoV-2 can be proteolytically cleaved into S1 (685 aa) and S2 (588 aa) subunits10. The S2 protein is well conserved among SARS-CoV-2 viruses and shares 99% identity with that of bat SARS-CoVs10. The vaccine design based on the S2 protein may boost the broad-spectrum antiviral effect and is worth testing in animal models. Antibodies against the conserved stem region of influenza hemagglutinin have been found to exhibit broadly cross-reactive immunity, but are less potent in neutralizing influenza A virus17. In contrast, the S1 subunit consists of the receptor-binding domain (RBD), which mediates virus entry into sensitive cells through the host angiotensin-converting enzyme 2 (ACE2) receptor18. The S1 protein of 2019-nCoV shares about 70% identity with that of human SARS-CoVs. The highest number of variations of amino acids in the RBD is located in the external subdomain, which is responsible for the direct interaction between virus and host receptor10,18. Blocking the initial entry of a virus is proposed as a successful strategy in controlling viral infection. Based on SARS vaccine development, most vaccine candidates target the S protein, which induces neutralizing antibody responses and stimulates a protective cellular immunity against SARS-CoVs12. Bukreyev et al.19 showed that immunization of African green monkeys with the full-length S protein of SARS-CoV protects monkeys from subsequent homologous SARS-CoV challenge. Administration of SARS-CoV RBD proteins can also induce highly potent neutralizing antibodies and long-term protective immunity in animal models20. Thus, the generation of antibodies targeting the S1 subunit of SARS-CoV-2 would be an important preventive and treatment strategy that can be tested further in suitable models before clinical trials10.