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Review

Advances in SARS-CoV-2 receptor-binding domain-based COVID-19 vaccines

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Pages 422-439 | Received 24 Jan 2023, Accepted 03 May 2023, Published online: 10 May 2023

Figures & data

Figure 1. SARS-CoV-2 virion and spike protein RBD. (a) Schematic structure of SARS-CoV-2 virion. (b) Structure of SARS-CoV-2 spike (S) protein. (left) Cryo-EM structure of SARS-CoV-2 S protein trimer (PDB 6VXX). The three subunits are colored in salmon, green and blue, respectively. (right) Close-up view of SARS-CoV-2 S receptor-binding domain (RBD). (c) Schematic structure of SARS-CoV-2 S protein. It contains S1 and S2 subunits. SP, signal peptide. NTD, N-terminal domain. RBM, receptor-binding motif. FP, fusion peptide. HR1 and HR2, heptad repeat 1 and 2. TM, transmembrane. CP, cytoplasmic tail.

Figure 1. SARS-CoV-2 virion and spike protein RBD. (a) Schematic structure of SARS-CoV-2 virion. (b) Structure of SARS-CoV-2 spike (S) protein. (left) Cryo-EM structure of SARS-CoV-2 S protein trimer (PDB 6VXX). The three subunits are colored in salmon, green and blue, respectively. (right) Close-up view of SARS-CoV-2 S receptor-binding domain (RBD). (c) Schematic structure of SARS-CoV-2 S protein. It contains S1 and S2 subunits. SP, signal peptide. NTD, N-terminal domain. RBM, receptor-binding motif. FP, fusion peptide. HR1 and HR2, heptad repeat 1 and 2. TM, transmembrane. CP, cytoplasmic tail.

Figure 2. Structures of SARS-CoV-2 RBD-receptor complexes. (a) Structures of SARS-CoV-2 receptor-binding domain (RBD) from wildtype (WT) strain (PDB 6M0J), Beta variant (PDB 7VX4), Delta variant (PDB 7TEW), Kappa variant (PDB 7TEZ), or Omicron variant (PDB 7×O9) in complex with human angiotensin-converting enzyme 2 (ACE2). (b) Structures of SARS-CoV-2 RBD in complex with ACE2 from non-human species. WT RBD-bat ACE2 complex (PDB 7C8J), WT RBD-horse ACE2 complex (PDB 7FC5), Omicron RBD-mouse ACE2 complex (PDB 7×O6), and Omicron RBD-civet ACE2 complex (PDB 7WSK) are shown.

Figure 2. Structures of SARS-CoV-2 RBD-receptor complexes. (a) Structures of SARS-CoV-2 receptor-binding domain (RBD) from wildtype (WT) strain (PDB 6M0J), Beta variant (PDB 7VX4), Delta variant (PDB 7TEW), Kappa variant (PDB 7TEZ), or Omicron variant (PDB 7×O9) in complex with human angiotensin-converting enzyme 2 (ACE2). (b) Structures of SARS-CoV-2 RBD in complex with ACE2 from non-human species. WT RBD-bat ACE2 complex (PDB 7C8J), WT RBD-horse ACE2 complex (PDB 7FC5), Omicron RBD-mouse ACE2 complex (PDB 7×O6), and Omicron RBD-civet ACE2 complex (PDB 7WSK) are shown.

Figure 3. Schematic map of SARS-CoV-2 infection and RBD vaccine-induced immune responses. (a) SARS-CoV-2 infection. SARS-CoV-2 infects host cells by binding to cellular angiotensin converting enzyme 2 (ACE2) receptor via the receptor-binding domain (RBD) fragment in the spike (S) protein. (b) RBD vaccine-induced immune responses. RBD vaccines activate antigen presenting cells such as dendritic cells, and elicit specific CD4+ and CD8+ T cells, which either help B cells to produce antibodies, or directly kill virus-infected cells. The elicited neutralizing antibodies block the binding of RBD to the ACE2 receptor, thereby inhibiting subsequent viral entry process.

Figure 3. Schematic map of SARS-CoV-2 infection and RBD vaccine-induced immune responses. (a) SARS-CoV-2 infection. SARS-CoV-2 infects host cells by binding to cellular angiotensin converting enzyme 2 (ACE2) receptor via the receptor-binding domain (RBD) fragment in the spike (S) protein. (b) RBD vaccine-induced immune responses. RBD vaccines activate antigen presenting cells such as dendritic cells, and elicit specific CD4+ and CD8+ T cells, which either help B cells to produce antibodies, or directly kill virus-infected cells. The elicited neutralizing antibodies block the binding of RBD to the ACE2 receptor, thereby inhibiting subsequent viral entry process.

Table 1. Representative SARS-CoV-2 RBD-based COVID-19 vaccines in preclinical developmenta.