Journal article
Glycosylated Receptor-Binding-Domain-Targeting Mucosal Vaccines Protect Against SARS-CoV-2 Omicron and MERS-CoV
Vaccines (Basel), Vol.13(3), 293
03/10/2025
DOI: 10.3390/vaccines13030293
PMCID: PMC11946235
PMID: 40266218
Abstract
Background. The pathogenic coronaviruses (CoVs) MERS-CoV and SARS-CoV-2, which are responsible for the MERS outbreak and the COVID-19 pandemic, respectively, continue to infect humans, with significant adverse outcomes. There is a continuing need to develop mucosal vaccines against these respiratory viral pathogens to prevent entry and replication at mucosal sites. The receptor-binding domain (RBD) of the CoV spike (S) protein is a critical vaccine target, and glycan masking is a unique approach for designing subunit vaccines with improved neutralizing activity. Methods. We evaluated the efficacy of mucosal immunity, broad neutralizing activity, and cross-protection afforded by a combined glycosylated mucosal subunit vaccine encoding the RBDs of the original SARS-CoV-2 strain (SARS2-WT-RBD), the Omicron-XBB.1.5 variant (SARS2-Omi-RBD), and MERS-CoV (MERS-RBD). Results. Intranasal administration of the three-RBD protein cocktail induced effective, durable IgA and systemic IgG antibodies specific for the S protein of these CoVs, thereby neutralizing infection by pseudotyped SARS-CoV-2-WT, Omicron-XBB.1.5, and MERS-CoV. The mucosal vaccine cocktail protected immunized mice from challenge with SARS-CoV-2 Omicron-XBB.1.5 and MERS-CoV, leading to a significant reduction in the viral titers in the lungs. By contrast, the individual glycosylated RBD proteins only induced such immune responses and neutralizing antibodies against either SARS-CoV-2 or MERS-CoV, protecting against subsequent challenge with either SARS-CoV-2 or MERS-CoV; they did not provide simultaneous protection against both CoVs. Conclusions. This study describes a unique strategy for designing efficacious mucosal subunit vaccines that induce durable mucosal immunity, cross-neutralizing activity, and cross-protection against SARS-CoV-2 and MERS-CoV, highlighting the potential for the design of mucosal vaccines against other pathogens.
Details
- Title: Subtitle
- Glycosylated Receptor-Binding-Domain-Targeting Mucosal Vaccines Protect Against SARS-CoV-2 Omicron and MERS-CoV
- Creators
- Xiaoqing Guan - Georgia State UniversityAbhishek K. Verma - University of IowaQian Liu - Georgia State UniversityMelissa Palacios - Georgia State UniversityAbby E. Odle - University of IowaStanley Perlman - University of IowaLanying Du - Georgia State University
- Resource Type
- Journal article
- Publication Details
- Vaccines (Basel), Vol.13(3), 293
- DOI
- 10.3390/vaccines13030293
- PMID
- 40266218
- PMCID
- PMC11946235
- NLM abbreviation
- Vaccines (Basel)
- ISSN
- 2076-393X
- eISSN
- 2076-393X
- Publisher
- MDPI
- Grant note
- National Institutes of Health
This research was funded by the National Institutes of Health (grant numbers R01AI139092 and R01AI137472).
- Language
- English
- Date published
- 03/10/2025
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9984800195502771
Metrics
7 Record Views