Since the first description of SARS-like coronavirus (SL-CoV) (Lau S K, et al., 2005; Li W, et al., 2005), there have been successive reports on the detection of this group of new coronaviruses in bats around the world (Lau S K, et al., 2010; Ren W, et al., 2006; Tang X C, et al., 2006; Yuan J, et al., 2010). A pathogenicity study using synthesized SL-CoV showed that it could cause disease in mice if it acquired a small fragment from SARS-CoV (Becker M M, et al., 2008). These works highlighted the potential for SL-CoV to spillover into non-bat mammals, including humans, and cause disease.
The SARS-CoV spike protein (SSARS) is responsible for receptor binding and is also a major target of neutralizing antibodies (He Y, 2006). Based on the significant sequence difference between the SL-CoV spike protein (SSL) and SSARS, it is no surprising to find that sera from SL-CoV positive failed to neutralize SARS-CoV (Li W, et al., 2005). In our previous study, we found that SL-CoV infected bat sera could recognize a HIV-pseudovirus carrying the SSL protein, but not a similar pseudovirus carrying a mutant SSL protein with its receptor binding region replaced by that from the SSARS protein (Zhou P, et al., 2009). From that study, we postulated that the major immunodominant neutralizing epitope may lie in this region of the SSL protein.
Using five truncated expressed proteins and a panel of SSL-specific mouse polyclonal and monoclonal antibodies, we identified two immunogenic determinants, one of which is located in a different region from those identified for SSARS. This is the first report to identify immunogenic determinants on SSL. The data presented here will be useful for future development of both diagnostics and vaccines against SL-CoV.
Identification of Immunogenic Determinants of the Spike Protein of SARS-like Coronavirus
- Received Date: 08 November 2012
- Accepted Date: 21 March 2013
Abstract: Bat SARS-like coronavirus (SL-CoV) has a genome organization almost identical to that of SARS-CoV, but the N-terminus of the Spike (S) proteins, which interacts with host receptor and is a major target of neutralizing antibodies against CoVs, of the two viruses has only 63-64% sequence identity. Although there have been reports studying the overall immunogenicity of SSL, knowledge on the precise location of immunodominant determinants for SSL is still lacking. In this study, using a series of truncated expressed SSL fragments and SSL specific mouse sera, we identified two immunogenic determinants for SSL. Importantly, one of the two regions seems to be located in a region not shared by known immunogenic determinants of the SSARS. This finding will be of potential use in future monitoring of SL-CoV infection in bats and spillover animals and in development of more effective vaccine to cover broad protection against this new group of coronaviruses.