Glycosylated Receptor-Binding-Domain-Targeting Mucosal Vaccines Protect Against SARS-CoV-2 Omicron and MERS-CoV
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...
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MDPI AG
2025-03-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/13/3/293 |
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| author | Xiaoqing Guan Abhishek K. Verma Qian Liu Melissa Palacios Abby E. Odle Stanley Perlman Lanying Du |
| author_facet | Xiaoqing Guan Abhishek K. Verma Qian Liu Melissa Palacios Abby E. Odle Stanley Perlman Lanying Du |
| author_sort | Xiaoqing Guan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-26fbd22f4a5e49599557d22adb446eca |
| institution | DOAJ |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-26fbd22f4a5e49599557d22adb446eca2025-08-20T02:43:10ZengMDPI AGVaccines2076-393X2025-03-0113329310.3390/vaccines13030293Glycosylated Receptor-Binding-Domain-Targeting Mucosal Vaccines Protect Against SARS-CoV-2 Omicron and MERS-CoVXiaoqing Guan0Abhishek K. Verma1Qian Liu2Melissa Palacios3Abby E. Odle4Stanley Perlman5Lanying Du6Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USADepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USAInstitute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USAInstitute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USADepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USADepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USAInstitute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USABackground. 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.https://www.mdpi.com/2076-393X/13/3/293pathogenic coronavirusCOVID-19SARS-CoV-2MERS-CoVreceptor-binding domainmucosal immunity |
| spellingShingle | Xiaoqing Guan Abhishek K. Verma Qian Liu Melissa Palacios Abby E. Odle Stanley Perlman Lanying Du Glycosylated Receptor-Binding-Domain-Targeting Mucosal Vaccines Protect Against SARS-CoV-2 Omicron and MERS-CoV Vaccines pathogenic coronavirus COVID-19 SARS-CoV-2 MERS-CoV receptor-binding domain mucosal immunity |
| title | Glycosylated Receptor-Binding-Domain-Targeting Mucosal Vaccines Protect Against SARS-CoV-2 Omicron and MERS-CoV |
| title_full | Glycosylated Receptor-Binding-Domain-Targeting Mucosal Vaccines Protect Against SARS-CoV-2 Omicron and MERS-CoV |
| title_fullStr | Glycosylated Receptor-Binding-Domain-Targeting Mucosal Vaccines Protect Against SARS-CoV-2 Omicron and MERS-CoV |
| title_full_unstemmed | Glycosylated Receptor-Binding-Domain-Targeting Mucosal Vaccines Protect Against SARS-CoV-2 Omicron and MERS-CoV |
| title_short | Glycosylated Receptor-Binding-Domain-Targeting Mucosal Vaccines Protect Against SARS-CoV-2 Omicron and MERS-CoV |
| title_sort | glycosylated receptor binding domain targeting mucosal vaccines protect against sars cov 2 omicron and mers cov |
| topic | pathogenic coronavirus COVID-19 SARS-CoV-2 MERS-CoV receptor-binding domain mucosal immunity |
| url | https://www.mdpi.com/2076-393X/13/3/293 |
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