Reconstituted Dry Powder Formulations of ZnO-Adjuvanted Ovalbumin Induce Equivalent Serum Antibody Responses to Ovalbumin Adjuvanted with Alhydrogel® or Cationic Adjuvant Formulation 01 (Caf®01)
Research output: Working paper › Preprint › Research
Standard
Reconstituted Dry Powder Formulations of ZnO-Adjuvanted Ovalbumin Induce Equivalent Serum Antibody Responses to Ovalbumin Adjuvanted with Alhydrogel® or Cationic Adjuvant Formulation 01 (Caf®01). / Hellfritzsch, Marie; Christensen, Dennis; Foged, Camilla; Scherließ, Regina; Thakur, Aneesh.
2023.Research output: Working paper › Preprint › Research
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - UNPB
T1 - Reconstituted Dry Powder Formulations of ZnO-Adjuvanted Ovalbumin Induce Equivalent Serum Antibody Responses to Ovalbumin Adjuvanted with Alhydrogel® or Cationic Adjuvant Formulation 01 (Caf®01)
AU - Hellfritzsch, Marie
AU - Christensen, Dennis
AU - Foged, Camilla
AU - Scherließ, Regina
AU - Thakur, Aneesh
N1 - Funding declaration: We acknowledge the support from the NordicPOP (patient-oriented products) consortium funded by the NordForsk program Nordic University Hub (grant number 85352) and the Independent Research Fund Denmark (grant numbers 4184-00422 and 9041-00198B to CF). MH was supported by the NordicPOP mobility grant, and AT was supported by the Independent Research Fund Denmark grants. Conflict of Interests: DC was employed by Statens Serum Institut, Denmark, which is a non-profit government research facility, of which the CAF® adjuvants are proprietary products. The other authors involved in this study have no conflicts of interest. Ethical Approval: All experimental work with mice was approved by the Danish National Experiment Inspectorate under permit 2016-15-0201-01026 and was performed in accordance with the European Community directive 86/609 for the care and use of laboratory animals.
PY - 2023
Y1 - 2023
N2 - Most licensed human vaccines are based on liquid dosage forms but have poor storage stability and require continuous and expensive cold-chain storage. In contrast, the use of solid vaccine dosage forms, produced by for example spray drying, extends shelf life and eliminates the need for a cold chain. Zinc oxide (ZnO)-based nanoparticles display immunomodulatory properties, but their adjuvant effect as a dry powder formulation is unknown. Here, we show that reconstituted dry powder formulations of ZnO particles containing the model antigen ovalbumin (OVA) induce antigen specific CD8+ T cells and humoral responses. By systematically varying the ratio between ZnO and mannitol during spray drying, we manufactured dry powder formulations of OVA-containing ZnO particles that displayed: (i) a spherical or wrinkled surface morphology, (ii) an aerodynamic diameter and particle size distribution optimal for deep lung deposition, and (iii) aerosolization properties suitable for lung delivery. Reconstituted dry powder formulations of ZnO particles were well-tolerated by Calu-3 lung epithelial cells. Furthermore, almost equivalent OVA-specific serum antibody responses were stimulated by reconstituted ZnO particles, OVA adjuvanted with Alhydrogel®, and OVA adjuvanted with the cationic adjuvant formulation 01 (CAF®01). However, reconstituted dry powder ZnO particles and OVA adjuvanted with Alhydrogel® induced significantly lower OVA-specific CD8+CD44+ T-cell responses in the spleen than OVA adjuvanted with CAF®01. Similarly, reconstituted dry powder ZnO particles activated significantly lower percentages of follicular helper T cells and germinal center B cells in the draining lymph nodes than OVA adjuvanted with CAF®01. Overall, our results show that reconstituted dry powder formulations of ZnO nanoparticles can induce antigen-specific antibodies and can be used in vaccines to enhance antigen specific humoral immune responses against subunit protein antigens.
AB - Most licensed human vaccines are based on liquid dosage forms but have poor storage stability and require continuous and expensive cold-chain storage. In contrast, the use of solid vaccine dosage forms, produced by for example spray drying, extends shelf life and eliminates the need for a cold chain. Zinc oxide (ZnO)-based nanoparticles display immunomodulatory properties, but their adjuvant effect as a dry powder formulation is unknown. Here, we show that reconstituted dry powder formulations of ZnO particles containing the model antigen ovalbumin (OVA) induce antigen specific CD8+ T cells and humoral responses. By systematically varying the ratio between ZnO and mannitol during spray drying, we manufactured dry powder formulations of OVA-containing ZnO particles that displayed: (i) a spherical or wrinkled surface morphology, (ii) an aerodynamic diameter and particle size distribution optimal for deep lung deposition, and (iii) aerosolization properties suitable for lung delivery. Reconstituted dry powder formulations of ZnO particles were well-tolerated by Calu-3 lung epithelial cells. Furthermore, almost equivalent OVA-specific serum antibody responses were stimulated by reconstituted ZnO particles, OVA adjuvanted with Alhydrogel®, and OVA adjuvanted with the cationic adjuvant formulation 01 (CAF®01). However, reconstituted dry powder ZnO particles and OVA adjuvanted with Alhydrogel® induced significantly lower OVA-specific CD8+CD44+ T-cell responses in the spleen than OVA adjuvanted with CAF®01. Similarly, reconstituted dry powder ZnO particles activated significantly lower percentages of follicular helper T cells and germinal center B cells in the draining lymph nodes than OVA adjuvanted with CAF®01. Overall, our results show that reconstituted dry powder formulations of ZnO nanoparticles can induce antigen-specific antibodies and can be used in vaccines to enhance antigen specific humoral immune responses against subunit protein antigens.
U2 - 10.2139/ssrn.4409016
DO - 10.2139/ssrn.4409016
M3 - Preprint
T3 - SSRN Electronic Journal
BT - Reconstituted Dry Powder Formulations of ZnO-Adjuvanted Ovalbumin Induce Equivalent Serum Antibody Responses to Ovalbumin Adjuvanted with Alhydrogel® or Cationic Adjuvant Formulation 01 (Caf®01)
ER -
ID: 359722642