Table 1 Properties of RBD-based vaccine immunogens compared to full-length S-protein immunogens.
From: Scientific rationale for developing potent RBD-based vaccines targeting COVID-19
Properties | RBD | S-protein | Comments |
|---|---|---|---|
Structure | 3° | 4° | Tertiary structure recognized by conformational nAb |
Neutralizing antibody titer | High | High | >90% Target RBD but Spike protein offers anti-NTD and anti-S2 nAb |
RBD epitopes | Yes | Yes | RBD epitopes appear to undergo convergent evolution and cross-protect against CoV-2 variants and other sarbecoviruses. |
NTD epitopes | No | Yes | NTD is showing deletions, insertions, and divergent substitutions |
Neutralizing : binding antibody ratio | High | Medium | Induction of nAb that contribute to efficacy (CoP) favors an immune-focused strategy |
CD4+ epitopes | Medium | High | RBD-specific immunity can be augmented by multimeric display (virus-like particles) and adjuvants |
CD8+ epitopes | Low | Low | Subunit approaches (S-protein and RBD) appear to be devoid of CD8+ T-cell responses. S-protein offers better coverage for cell-mediated immunity (CMI). |
B-cell memory | High | High | RBD-specific memory B cells show evidence of somatic hypermutation, which increases breadth of neutralization |
Antibody persistence | Yes | Yes | Demonstrated >6 months (e.g., SK bioscience RBD-np and Pfizer-BioNTech S-protein vaccines) |
NHP efficacy | High | High | Proof-of-concept demonstrated against upper and lower respiratory tract infection and disease |
Clinical efficacy | Yes | Yes | 15 S-protein-based vaccines have reported ≥50% efficacy, with variations depending on the dominant viral variant. News reports of >90% for two Cuban RBD-based vaccines. |
Supply volume | High | Medium | COVAX has negotiated favorable access terms for RBD vaccine candidates |
Cost | Low | Medium | COGs low as produced by developing country vaccine manufacturers |
