A cGAMP‐Containing Hydrogel for Prolonged SARS‐CoV‐2 Receptor‐Binding Domain Subunit Vaccine Exposure Induces a Broad and Potent Humoral Response
The receptor‐binding domain (RBD) of the SARS‐CoV‐2 virus spike protein has emerged as a promising target for the generation of neutralizing antibodies. Although the RBD subunit is more stable than its encoding mRNA, RBD is poorly immunogenic. It is hypothesized that this limitation can be overcome...
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| Format: | Article |
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Wiley-VCH
2025-01-01
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| Series: | Advanced NanoBiomed Research |
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| Online Access: | https://doi.org/10.1002/anbr.202400077 |
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| author | Volker Böhnert Emily C. Gale Lauren J. Lahey Jerry Yan Abigail E. Powell Ben S. Ou Jacqueline A. Carozza Lingyin Li Eric A. Appel |
| author_facet | Volker Böhnert Emily C. Gale Lauren J. Lahey Jerry Yan Abigail E. Powell Ben S. Ou Jacqueline A. Carozza Lingyin Li Eric A. Appel |
| author_sort | Volker Böhnert |
| collection | DOAJ |
| description | The receptor‐binding domain (RBD) of the SARS‐CoV‐2 virus spike protein has emerged as a promising target for the generation of neutralizing antibodies. Although the RBD subunit is more stable than its encoding mRNA, RBD is poorly immunogenic. It is hypothesized that this limitation can be overcome by sustained coadministration with a more potent and optimized adjuvant than standard adjuvants. One such candidate adjuvant, cGAMP, exhibits promising potency via activation of the antiviral STING pathway. Unfortunately, delivery of cGAMP as a therapeutic exhibits poor performance due to poor pharmacokinetics and pharmacodynamics from rapid excretion and degradation. To overcome these limitations, it is sought to create an artificial immunological niche enabling the slow release of cGAMP and RBD to mimic natural infections in which immune‐activating molecules are colocalized with antigen. Specifically, through coencapsulation of cGAMP and RBD in an injectable polymer‐nanoparticle (PNP) hydrogel, the cGAMP‐adjuvanted hydrogel vaccine elicits more potent, durable, and broad antibody responses with improved neutralization as compared to dose‐matched bolus controls and hydrogel‐based vaccines lacking cGAMP. The cGAMP‐adjuvanted hydrogel platform can be further explored for the delivery of other antigens to enhance immunity against a broad range of pathogens. |
| format | Article |
| id | doaj-art-410306ed071d42cd922383763ea085ad |
| institution | Kabale University |
| issn | 2699-9307 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley-VCH |
| record_format | Article |
| series | Advanced NanoBiomed Research |
| spelling | doaj-art-410306ed071d42cd922383763ea085ad2025-01-07T09:13:09ZengWiley-VCHAdvanced NanoBiomed Research2699-93072025-01-0151n/an/a10.1002/anbr.202400077A cGAMP‐Containing Hydrogel for Prolonged SARS‐CoV‐2 Receptor‐Binding Domain Subunit Vaccine Exposure Induces a Broad and Potent Humoral ResponseVolker Böhnert0Emily C. Gale1Lauren J. Lahey2Jerry Yan3Abigail E. Powell4Ben S. Ou5Jacqueline A. Carozza6Lingyin Li7Eric A. Appel8Department of Materials Science and Engineering Stanford University Stanford CA 94305 USADepartment of Materials Science and Engineering Stanford University Stanford CA 94305 USAStanford ChEM‐H Program Stanford University Stanford CA 94305 USADepartment of Bioengineering Stanford University Stanford CA 94305 USADepartment of Biochemistry Stanford University School of Medicine Stanford CA 94305 USADepartment of Bioengineering Stanford University Stanford CA 94305 USAStanford ChEM‐H Program Stanford University Stanford CA 94305 USADepartment of Biochemistry Stanford University School of Medicine Stanford CA 94305 USADepartment of Materials Science and Engineering Stanford University Stanford CA 94305 USAThe receptor‐binding domain (RBD) of the SARS‐CoV‐2 virus spike protein has emerged as a promising target for the generation of neutralizing antibodies. Although the RBD subunit is more stable than its encoding mRNA, RBD is poorly immunogenic. It is hypothesized that this limitation can be overcome by sustained coadministration with a more potent and optimized adjuvant than standard adjuvants. One such candidate adjuvant, cGAMP, exhibits promising potency via activation of the antiviral STING pathway. Unfortunately, delivery of cGAMP as a therapeutic exhibits poor performance due to poor pharmacokinetics and pharmacodynamics from rapid excretion and degradation. To overcome these limitations, it is sought to create an artificial immunological niche enabling the slow release of cGAMP and RBD to mimic natural infections in which immune‐activating molecules are colocalized with antigen. Specifically, through coencapsulation of cGAMP and RBD in an injectable polymer‐nanoparticle (PNP) hydrogel, the cGAMP‐adjuvanted hydrogel vaccine elicits more potent, durable, and broad antibody responses with improved neutralization as compared to dose‐matched bolus controls and hydrogel‐based vaccines lacking cGAMP. The cGAMP‐adjuvanted hydrogel platform can be further explored for the delivery of other antigens to enhance immunity against a broad range of pathogens.https://doi.org/10.1002/anbr.202400077COVID‐19drug deliverySARS‐CoV‐2stimulators of interferon genesvaccines |
| spellingShingle | Volker Böhnert Emily C. Gale Lauren J. Lahey Jerry Yan Abigail E. Powell Ben S. Ou Jacqueline A. Carozza Lingyin Li Eric A. Appel A cGAMP‐Containing Hydrogel for Prolonged SARS‐CoV‐2 Receptor‐Binding Domain Subunit Vaccine Exposure Induces a Broad and Potent Humoral Response Advanced NanoBiomed Research COVID‐19 drug delivery SARS‐CoV‐2 stimulators of interferon genes vaccines |
| title | A cGAMP‐Containing Hydrogel for Prolonged SARS‐CoV‐2 Receptor‐Binding Domain Subunit Vaccine Exposure Induces a Broad and Potent Humoral Response |
| title_full | A cGAMP‐Containing Hydrogel for Prolonged SARS‐CoV‐2 Receptor‐Binding Domain Subunit Vaccine Exposure Induces a Broad and Potent Humoral Response |
| title_fullStr | A cGAMP‐Containing Hydrogel for Prolonged SARS‐CoV‐2 Receptor‐Binding Domain Subunit Vaccine Exposure Induces a Broad and Potent Humoral Response |
| title_full_unstemmed | A cGAMP‐Containing Hydrogel for Prolonged SARS‐CoV‐2 Receptor‐Binding Domain Subunit Vaccine Exposure Induces a Broad and Potent Humoral Response |
| title_short | A cGAMP‐Containing Hydrogel for Prolonged SARS‐CoV‐2 Receptor‐Binding Domain Subunit Vaccine Exposure Induces a Broad and Potent Humoral Response |
| title_sort | cgamp containing hydrogel for prolonged sars cov 2 receptor binding domain subunit vaccine exposure induces a broad and potent humoral response |
| topic | COVID‐19 drug delivery SARS‐CoV‐2 stimulators of interferon genes vaccines |
| url | https://doi.org/10.1002/anbr.202400077 |
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