tetano
Editor, Senior Moderator
Adv Healthc Mater
. 2021 Nov 10;e2101714.
doi: 10.1002/adhm.202101714. Online ahead of print.
Sustained Delivery of SARS-CoV-2 RBD Subunit Vaccine using a High Affinity Injectable Hydrogel Scaffold
Jing Chen[SUP] 1 2 [/SUP], Bo Wang[SUP] 2 [/SUP], Julia S Caserto[SUP] 3 [/SUP], Kaavian Shariati[SUP] 2 [/SUP], Peng Cao[SUP] 1 [/SUP], Yang Pan[SUP] 1 [/SUP], Qixuan Xu[SUP] 1 [/SUP], Minglin Ma[SUP] 2 [/SUP]
Affiliations
Abstract
The receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein that mediates viral entry into host cells is a good candidate immunogen for vaccine development against coronavirus disease 2019 (COVID-19). As a result of its small size, most preclinical and early clinical efforts have focused on multimerizing RBD on various formats of nanoparticles to increase its immunogenicity. Using an easily administered injectable hydrogel scaffold that was rationally designed for enhanced retainment of RBD, we demonstrated an alternative and facile approach for boosting RBD immunogenicity in mice. Prolonged delivery of poly (I:C) adjuvanted RBD by the hydrogel scaffold resulted in sustained exposure to lymphoid tissues, which elicited serum IgG titers comparable to those induced by three bolus injections, but more long-lasting and polarized toward T[SUB]H[/SUB] 1-mediated IgG2b. The hydrogel scaffold induced potent germinal center (GC) reactions, correlating with RBD-specific antibody generation, as well as robust type 1 T cell responses. Besides being an enduring RBD reservoir, the hydrogel scaffold became a local inflammatory niche for innate immune cell activation. Collectively, our injectable hydrogel scaffold provides a simple, practical, and inexpensive means to enhance the efficacy of RBD-based subunit vaccines against COVID-19 and may be applicable to other circulating and emerging pathogens. This article is protected by copyright. All rights reserved.
Keywords: SARS-CoV-2 RBD; cellular immunity; germinal center; humoral immunity; injectable hydrogel scaffold; sustained release; vaccines.
. 2021 Nov 10;e2101714.
doi: 10.1002/adhm.202101714. Online ahead of print.
Sustained Delivery of SARS-CoV-2 RBD Subunit Vaccine using a High Affinity Injectable Hydrogel Scaffold
Jing Chen[SUP] 1 2 [/SUP], Bo Wang[SUP] 2 [/SUP], Julia S Caserto[SUP] 3 [/SUP], Kaavian Shariati[SUP] 2 [/SUP], Peng Cao[SUP] 1 [/SUP], Yang Pan[SUP] 1 [/SUP], Qixuan Xu[SUP] 1 [/SUP], Minglin Ma[SUP] 2 [/SUP]
Affiliations
- PMID: 34755476
- DOI: 10.1002/adhm.202101714
Abstract
The receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein that mediates viral entry into host cells is a good candidate immunogen for vaccine development against coronavirus disease 2019 (COVID-19). As a result of its small size, most preclinical and early clinical efforts have focused on multimerizing RBD on various formats of nanoparticles to increase its immunogenicity. Using an easily administered injectable hydrogel scaffold that was rationally designed for enhanced retainment of RBD, we demonstrated an alternative and facile approach for boosting RBD immunogenicity in mice. Prolonged delivery of poly (I:C) adjuvanted RBD by the hydrogel scaffold resulted in sustained exposure to lymphoid tissues, which elicited serum IgG titers comparable to those induced by three bolus injections, but more long-lasting and polarized toward T[SUB]H[/SUB] 1-mediated IgG2b. The hydrogel scaffold induced potent germinal center (GC) reactions, correlating with RBD-specific antibody generation, as well as robust type 1 T cell responses. Besides being an enduring RBD reservoir, the hydrogel scaffold became a local inflammatory niche for innate immune cell activation. Collectively, our injectable hydrogel scaffold provides a simple, practical, and inexpensive means to enhance the efficacy of RBD-based subunit vaccines against COVID-19 and may be applicable to other circulating and emerging pathogens. This article is protected by copyright. All rights reserved.
Keywords: SARS-CoV-2 RBD; cellular immunity; germinal center; humoral immunity; injectable hydrogel scaffold; sustained release; vaccines.