Id |
Subject |
Object |
Predicate |
Lexical cue |
T266 |
0-38 |
Sentence |
denotes |
MERS-CoV Subunit Vaccines Based on RBD |
T267 |
39-255 |
Sentence |
denotes |
Numerous MERS-CoV RBD-based subunit vaccines have been developed and extensively evaluated in available animal models since the emergence of MERS-CoV (Table 2) (Du et al., 2013c; Tai et al., 2017; Zhou et al., 2018). |
T268 |
256-499 |
Sentence |
denotes |
In general, these subunit vaccines have strong immunogenicity and are capable of inducing high neutralizing antibodies and/or protection against MERS-CoV infection (Ma et al., 2014b; Zhang et al., 2016; Tai et al., 2017; Wang Y. et al., 2017). |
T269 |
500-627 |
Sentence |
denotes |
Most subunit vaccines based on the MERS-CoV RBD have been described in detail in a previous review article (Zhou et al., 2019). |
T270 |
628-811 |
Sentence |
denotes |
In this section, we will briefly introduce these RBD-targeting MERS vaccines, and compare their functionality, antigenicity, immunogenicity, and protection against MERS-CoV infection. |
T271 |
812-1021 |
Sentence |
denotes |
Co-crystallographic analyses of MERS-CoV RBD and/or RBD/DPP4 complexes have confirmed that the RBD is attributed to residues 367–588 (Chen et al., 2013) or 367–606 (Lu et al., 2013) in the MERS-CoV S1 subunit. |
T272 |
1022-1246 |
Sentence |
denotes |
Indeed, a recombinant MERS-CoV RBD (rRBD) fragment (residues 367–606) elicits RBD-specific antibody and cellular immune responses and neutralizing antibodies in mice and/or non-human primates (NHPs) (Lan et al., 2014, 2015). |
T273 |
1247-1418 |
Sentence |
denotes |
However, it only partially protects NHPs from MERS-CoV infection by alleviating pneumonia and clinical manifestations, as well as decreasing viral load (Lan et al., 2015). |
T274 |
1419-1727 |
Sentence |
denotes |
In addition, an RBD protein fragment containing MERS-CoV S residues 377–622 fused with the Fc tag of human IgG can induce MERS-CoV S1- and/or RBD-specific humoral and cellular immune responses in the immunized mice with neutralizing activity against MERS-CoV infection (Du et al., 2013c; Jiang et al., 2013). |
T275 |
1728-2076 |
Sentence |
denotes |
However, after comparing several versions of MERS-CoV RBD fragments with different lengths, it was found that a truncated RBD (residues 377–588) had the highest DPP4-binding affinity and induced the highest-titer IgG antibodies and neutralizing antibodies against MERS-CoV, identifying its role as a critical neutralizing domain (Ma et al., 2014b). |
T276 |
2077-2501 |
Sentence |
denotes |
Subsequently, several MERS-CoV subunit vaccines have been designed based on the identified critical neutralizing domain of RBD fragment, including those expressed in a stable CHO cell line (S377-588-Fc), fusing with a trimeric motif foldon (RBD-Fd), or containing single or multiple mutations in the RBD of representative human and camel strains from the 2012–2015 MERS outbreaks (Tai et al., 2016, 2017; Nyon et al., 2018). |
T277 |
2502-2837 |
Sentence |
denotes |
These RBD proteins maintain good conformation, functionality, antigenicity, and immunogenicity, with ability to bind the DPP4 receptor and RBD-specific neutralizing mAbs and to elicit robust neutralizing antibodies cross-neutralizing multiple strains of MERS pseudoviruses and live MERS-CoV (Tai et al., 2016, 2017; Nyon et al., 2018). |
T278 |
2838-3508 |
Sentence |
denotes |
It is noted that the wild-type MERS-CoV RBD proteins consisting of the identified critical neutralizing domain confer partial protection of hDPP4-transgenic (hDPP4-Tg) mice from MERS-CoV infection without causing immunological toxicity or eosinophilic immune enhancement (Tai et al., 2016; Wang Y. et al., 2017; Nyon et al., 2018); nevertheless, a structurally designed mutant version of such RBD protein with a non-neutralizing epitope masked (T579N) preserves intact conformation and significantly improves overall neutralizing activity and protective efficacy, resulting in the full protection of hDPP4-Tg mice against high-dose MERS-CoV challenge (Du et al., 2016a). |
T279 |
3509-3718 |
Sentence |
denotes |
The above studies indicate that protein lengths to be chosen as MERS-CoV subunit vaccines and/or structure-based vaccine design can impact on the immunogenicity and/or protection of RBD-based subunit vaccines. |