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Barbey, Clara ; Su, Jinpeng ; Billmeier, Martina ; Stefan, Nadine ; Bester, Romina ; Carnell, George ; Temperton, Nigel ; Heeney, Jonathan L. ; Protzer, Ulrike ; Breunig, Miriam ; Wagner, Ralf ; Peterhoff, David

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 , Heeney, Jonathan L. , Protzer, Ulrike, Breunig, Miriam , Wagner, Ralf und Peterhoff, David (2023) Immunogenicity of a silica nanoparticle-based SARS-CoV-2 vaccine in mice. European Journal of Pharmaceutics and Biopharmaceutics 192, S. 41-55.

Veröffentlichungsdatum dieses Volltextes: 09 Nov 2023 12:09
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.54977


Zusammenfassung

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 ...

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 vaccinemediated both humoral and cell-mediated immune responses. Based on this, we hypothesized that SARS-CoV2 RBD as immunogen would benefit from being presented to the immune system via silica nanoparticles (SiNPs). 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.



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Details

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftEuropean Journal of Pharmaceutics and Biopharmaceutics
Verlag:ELSEVIER
Ort der Veröffentlichung:AMSTERDAM
Band:192
Seitenbereich:S. 41-55
Datum27 September 2023
InstitutionenMedizin > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Identifikationsnummer
WertTyp
10.1016/j.ejpb.2023.09.015DOI
Stichwörter / KeywordsMONOPHOSPHORYL-LIPID-A; T-CELL; ANTIBODY-RESPONSES; DENDRITIC CELLS; COVID-19; DELIVERY; IMMUNITY; CARRIERS; DESIGN; Silica nanoparticles; SARS-CoV-2; COVID-19 vaccine; Receptor-binding domain; RBD; Mouse immunization study; Humoral immune response; Cellular immune response
Dewey-Dezimal-Klassifikation600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenJa
URN der UB Regensburgurn:nbn:de:bvb:355-epub-549775
Dokumenten-ID54977

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