Publication date: May 20, 2025
(1) Background: The currently circulating variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits resistance to antibodies induced by vaccines. The World Health Organization recommended the use of monovalent XBB. 1 sublineages (e. g., XBB. 1.5) as an antigenic component in 2023. (2) Objective: In this study, we aimed to develop vaccines based on the XBB. 1.5 receptor-binding domain (RBD) to combat the recently emerged SARS-CoV-2 XBB and JN. 1 variants, as well as previously circulating variants. (3) Methods: Glycoengineered Pichia pastoris was utilized to produce a recombinant XBB. 1.5 RBD protein with mammalian-like and fucose-free N-glycosylation. The XBB. 1.5 RBD was mixed with Al(OH):CpG adjuvants to prepare monovalent vaccines. Thereafter, the XBB. 1.5 RBD was mixed with the Beta (B. 1.351), Delta (B. 1.617. 2), or Omicron (BA. 2) RBDs (1:1 ratio), along with Al(OH):CpG, to prepare bivalent vaccines. BALB/c mice were immunized with the monovalent and bivalent vaccines. Neutralizing antibody titers were assessed via pseudovirus and authentic virus assays; humoral immune responses were analyzed by RBD-binding IgG subtypes. (4) Results: The monovalent vaccine induced higher neutralizing antibody titers against Delta, BA. 2, XBB. 1.5, and JN. 1 compared to those in mice immunized solely with Al(OH):CpG, as demonstrated by pseudovirus virus assays. The XBB. 1.5/Delta RBD and XBB. 1.5/Beta RBD-based bivalent vaccines provided potent protection against the BA. 2, XBB. 1.5, JN. 1, and KP. 2 variants, as well as the previously circulating Delta and Beta variants. All monovalent and bivalent vaccines induced high levels of RBD-binding IgG (IgG1, IgG2a, IgG2b, and IgG3) antibodies in mice, suggesting that they elicited robust humoral immune responses. The serum samples from mice immunized with the XBB. 1.5 RBD-based and XBB. 1.5/Delta RBD-based vaccines could neutralize the authentic XBB. 1.16 virus. (5) Conclusions: The XBB. 1.5/Beta and XBB. 1.5/Delta RBD-based bivalent vaccines are considered as potential candidates for broad-spectrum vaccines against SARS-CoV-2 variants.
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| Concepts | Keywords |
|---|---|
| Free | bivalent vaccine |
| Glycosylation | glycoengineered yeast |
| Mice | monovalent vaccine |
| Pastoris | RBD |
| Vaccines | SARS-CoV-2 |
| subunit vaccine |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | IDO | protein |
| drug | DRUGBANK | Coenzyme M |
| pathway | REACTOME | Reproduction |
| disease | MESH | COVID 19 pandemic |
| pathway | KEGG | Virion |
| disease | IDO | host |
| drug | DRUGBANK | Amino acids |
| drug | DRUGBANK | Tropicamide |
| disease | IDO | infectivity |
| drug | DRUGBANK | Mannose |
| drug | DRUGBANK | Aluminum hydroxide |
| drug | DRUGBANK | Aluminium |
| drug | DRUGBANK | Glutamic Acid |
| disease | IDO | reagent |
| disease | IDO | colony |
| disease | IDO | quality |
| drug | DRUGBANK | Sodium lauryl sulfate |
| drug | DRUGBANK | Phosphate ion |
| drug | DRUGBANK | Ethanol |
| disease | IDO | blood |
| disease | IDO | assay |
| disease | MESH | Mutation frequency |
| disease | IDO | production |
| disease | MESH | infections |
| disease | MESH | Allergy |
| disease | IDO | cell |
| drug | DRUGBANK | Guanosine |
| disease | MESH | breakthrough infection |
| drug | DRUGBANK | (S)-Des-Me-Ampa |
| disease | IDO | bacteria |
| disease | MESH | influenza |
| drug | DRUGBANK | Carboxyamidotriazole |