Assessing the Immunomodulatory Effect of Size on the Uptake and Immunogenicity of Influenza- and Hepatitis B Subunit Vaccines In Vitro
Viral subunit vaccines are a safer and more tolerable alternative to whole inactivated virus vaccines. However, they often come with limited efficacy, necessitating the use of adjuvants. Using free and particle-bound viral antigens, we assessed whether size affects the uptake of those antigens by hu...
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MDPI AG
2022-07-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/7/887 |
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| author | Rick Heida Philip A. Born Gabriela Tapia-Calle Henderik W. Frijlink Anna Salvati Anke L. W. Huckriede Wouter L. J. Hinrichs |
| author_facet | Rick Heida Philip A. Born Gabriela Tapia-Calle Henderik W. Frijlink Anna Salvati Anke L. W. Huckriede Wouter L. J. Hinrichs |
| author_sort | Rick Heida |
| collection | DOAJ |
| description | Viral subunit vaccines are a safer and more tolerable alternative to whole inactivated virus vaccines. However, they often come with limited efficacy, necessitating the use of adjuvants. Using free and particle-bound viral antigens, we assessed whether size affects the uptake of those antigens by human monocyte-derived dendritic cells (Mo-DCs) and whether differences in uptake affect their capacity to stimulate cytokine production by T cells. To this end, influenza antigens and hepatitis B surface antigen (HBsAg) were covalently conjugated to polystyrene particles of 500 nm and 3 μm. Cellular uptake of the antigens, either unconjugated or conjugated, and their capacity to stimulate T cells within a population of human peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry. Conjugation of both antigens to particles significantly increased their uptake by Mo-DCs. Moreover, both the 500 nm and 3 μm influenza conjugates induced significantly higher numbers of cytokine-producing CD4<sup>+</sup> T cells and induced increased production of the pro-inflammatory cytokines IFNγ and TNFα. In contrast, conjugation of HBsAg to particles did not notably affect the T cell response. In conclusion, conjugation of antigen to 500 nm and 3 μm particles leads to increased antigen uptake by human Mo-DCs, although the capacity of such conjugates to induce T cell stimulation likely depends on the immunological status of the PBMC donor. |
| first_indexed | 2024-03-09T06:04:39Z |
| format | Article |
| id | doaj.art-b80fc80388764e589a795e4b84336c84 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T06:04:39Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-b80fc80388764e589a795e4b84336c842023-12-03T12:05:47ZengMDPI AGPharmaceuticals1424-82472022-07-0115788710.3390/ph15070887Assessing the Immunomodulatory Effect of Size on the Uptake and Immunogenicity of Influenza- and Hepatitis B Subunit Vaccines In VitroRick Heida0Philip A. Born1Gabriela Tapia-Calle2Henderik W. Frijlink3Anna Salvati4Anke L. W. Huckriede5Wouter L. J. Hinrichs6Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Pharmaceutical Technology and Biopharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The NetherlandsDepartment of Pharmaceutical Technology and Biopharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Nanomedicine and Drug Targeting, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The NetherlandsDepartment of Pharmaceutical Technology and Biopharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsViral subunit vaccines are a safer and more tolerable alternative to whole inactivated virus vaccines. However, they often come with limited efficacy, necessitating the use of adjuvants. Using free and particle-bound viral antigens, we assessed whether size affects the uptake of those antigens by human monocyte-derived dendritic cells (Mo-DCs) and whether differences in uptake affect their capacity to stimulate cytokine production by T cells. To this end, influenza antigens and hepatitis B surface antigen (HBsAg) were covalently conjugated to polystyrene particles of 500 nm and 3 μm. Cellular uptake of the antigens, either unconjugated or conjugated, and their capacity to stimulate T cells within a population of human peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry. Conjugation of both antigens to particles significantly increased their uptake by Mo-DCs. Moreover, both the 500 nm and 3 μm influenza conjugates induced significantly higher numbers of cytokine-producing CD4<sup>+</sup> T cells and induced increased production of the pro-inflammatory cytokines IFNγ and TNFα. In contrast, conjugation of HBsAg to particles did not notably affect the T cell response. In conclusion, conjugation of antigen to 500 nm and 3 μm particles leads to increased antigen uptake by human Mo-DCs, although the capacity of such conjugates to induce T cell stimulation likely depends on the immunological status of the PBMC donor.https://www.mdpi.com/1424-8247/15/7/887dendritic cellsdrug delivery systemsflow cytometryhepatitis B virushuman peripheral blood mononuclear cellsinfluenza virus |
| spellingShingle | Rick Heida Philip A. Born Gabriela Tapia-Calle Henderik W. Frijlink Anna Salvati Anke L. W. Huckriede Wouter L. J. Hinrichs Assessing the Immunomodulatory Effect of Size on the Uptake and Immunogenicity of Influenza- and Hepatitis B Subunit Vaccines In Vitro Pharmaceuticals dendritic cells drug delivery systems flow cytometry hepatitis B virus human peripheral blood mononuclear cells influenza virus |
| title | Assessing the Immunomodulatory Effect of Size on the Uptake and Immunogenicity of Influenza- and Hepatitis B Subunit Vaccines In Vitro |
| title_full | Assessing the Immunomodulatory Effect of Size on the Uptake and Immunogenicity of Influenza- and Hepatitis B Subunit Vaccines In Vitro |
| title_fullStr | Assessing the Immunomodulatory Effect of Size on the Uptake and Immunogenicity of Influenza- and Hepatitis B Subunit Vaccines In Vitro |
| title_full_unstemmed | Assessing the Immunomodulatory Effect of Size on the Uptake and Immunogenicity of Influenza- and Hepatitis B Subunit Vaccines In Vitro |
| title_short | Assessing the Immunomodulatory Effect of Size on the Uptake and Immunogenicity of Influenza- and Hepatitis B Subunit Vaccines In Vitro |
| title_sort | assessing the immunomodulatory effect of size on the uptake and immunogenicity of influenza and hepatitis b subunit vaccines in vitro |
| topic | dendritic cells drug delivery systems flow cytometry hepatitis B virus human peripheral blood mononuclear cells influenza virus |
| url | https://www.mdpi.com/1424-8247/15/7/887 |
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