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Immunogenicity of a silica nanoparticle-based SARS-CoV-2 vaccine in mice

Barbey, Clara, Su, Jinpeng, Billmeier, Martina, Stefan, Nadine, Bester, Romina, Carnell, George, Temperton, Nigel J., Heeney, Jonathan, Protzer, Ulrike, Breunig, Miriam, and others. (2023) Immunogenicity of a silica nanoparticle-based SARS-CoV-2 vaccine in mice. European Journal of Pharmaceutics and Biopharmaceutics, . ISSN 0939-6411. (doi:10.1016/j.ejpb.2023.09.015) (KAR id:103068)

Abstract

Safe and effective vaccines have been regarded early on as critical in combating the COVID-19 pandemic. Among the deployed vaccine platforms, subunit vaccines have a particularly good safety profile but may suffer from a lower immunogenicity compared to mRNA based or viral vector vaccines. In fact, this phenomenon has also been observed for SARS-CoV-2 subunit vaccines comprising the receptor-binding domain (RBD) of the spike (S) protein. Therefore, RBD-based vaccines have to rely on additional measures to enhance the immune response. It is well accepted that displaying antigens on nanoparticles can improve the quantity and quality of vaccine-mediated both humoral and cell-mediated immune responses. Based on this, we hypothesized that SARS-CoV-2 RBD as immunogen would benefit from being presented to the immune system via silica nanoparticles (SiNP). Herein we describe the preparation, in vitro characterization, antigenicity and in vivo immunogenicity of SiNPs decorated with properly oriented RBD in mice.

We found our RBD-SiNP conjugates show narrow, homogeneous particle distribution with optimal size of about 100 nm for efficient transport to and into the lymph node. The colloidal stability and binding of the antigen was stable for at least 4 months at storage- and in vivo-temperatures. The antigenicity of the RBD was maintained upon binding to the SiNP surface, and the receptor-binding motif was readily accessible due to the spatial orientation of the RBD. The particles were efficiently taken up in vitro by antigen-presenting cells. In a mouse immunization study using an mRNA vaccine and spike protein as benchmarks, we found that the SiNP formulation was able to elicit a stronger RBD-specific humoral response compared to the soluble protein. For the adjuvanted RBD-SiNP we found strong S-specific multifunctional CD4+ T cell responses, a balanced T helper response, improved auto- and heterologous virus neutralization capacity, and increased serum avidity, suggesting increased affinity maturation.

In summary, our results provide further evidence for the possibility of optimizing the cellular and humoral immune response through antigen presentation on SiNP.

Item Type: Article
DOI/Identification number: 10.1016/j.ejpb.2023.09.015
Additional information: For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Funders: Medical Research Council (https://ror.org/03x94j517)
Depositing User: Nigel Temperton
Date Deposited: 29 Sep 2023 13:57 UTC
Last Modified: 12 Jan 2024 09:28 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/103068 (The current URI for this page, for reference purposes)

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