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Published on: July 25, 2022
Glycosylated Receptor-Binding-Domain-Targeting Mucosal Vaccines Protect Against SARS-CoV-2 Omicron and MERS-CoV
Xiaoqing Guan1, Abhishek K Verma2, Qian Liu1
1Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
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.
Insights
A novel mucosal vaccine combining receptor-binding domains from SARS-CoV-2 and MERS-CoV elicits broad immunity. This intranasal vaccine provides durable protection against multiple coronavirus variants and MERS-CoV, reducing viral lung titers in mice.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- Pathogenic coronaviruses (CoVs), including MERS-CoV and SARS-CoV-2, cause significant human illness.
- Developing mucosal vaccines is crucial to prevent respiratory viral entry and replication.
- Glycan masking of receptor-binding domains (RBDs) is a strategy for enhancing subunit vaccine efficacy.
Purpose of the Study:
- To evaluate a novel glycosylated mucosal subunit vaccine.
- The vaccine combines RBDs from SARS-CoV-2 (wild-type and Omicron-XBB.1.5) and MERS-CoV.
- To assess mucosal immunity, neutralizing activity, and cross-protection.
Main Methods:
- Intranasal administration of a three-RBD protein cocktail vaccine.
- Evaluation of IgA and IgG antibody responses.
- Testing neutralization and protection against SARS-CoV-2 (WT, Omicron-XBB.1.5) and MERS-CoV challenge in mice.
Main Results:
- The three-RBD vaccine induced durable IgA and IgG antibodies against multiple CoVs.
- Intranasal vaccination neutralized SARS-CoV-2 (WT, Omicron-XBB.1.5) and MERS-CoV.
- Vaccinated mice showed reduced viral lung titers after challenge with SARS-CoV-2 Omicron-XBB.1.5 and MERS-CoV.
Conclusions:
- A unique strategy for designing effective mucosal subunit vaccines.
- The vaccine induces durable mucosal immunity and cross-neutralizing activity.
- Demonstrates potential for developing mucosal vaccines against various respiratory pathogens.
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