Heida Rick, Born Philip A, Tapia-Calle Gabriela, Frijlink Henderik W, Salvati Anna, Huckriede Anke L W, Hinrichs Wouter L J
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, 9713 AV Groningen, The Netherlands.
Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands.
Pharmaceuticals (Basel). 2022 Jul 18;15(7):887. doi: 10.3390/ph15070887.
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 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.
病毒亚单位疫苗是比全灭活病毒疫苗更安全、耐受性更好的替代品。然而，它们的疗效往往有限，因此需要使用佐剂。我们使用游离和颗粒结合的病毒抗原，评估了颗粒大小是否会影响人单核细胞衍生树突状细胞（Mo-DC）对这些抗原的摄取，以及摄取差异是否会影响它们刺激T细胞产生细胞因子的能力。为此，将流感抗原和乙型肝炎表面抗原（HBsAg）共价偶联到500 nm和3 μm的聚苯乙烯颗粒上。通过流式细胞术测量未偶联或偶联抗原的细胞摄取情况，以及它们在人外周血单核细胞（PBMC）群体中刺激T细胞的能力。两种抗原与颗粒的偶联均显著增加了Mo-DC对它们的摄取。此外，500 nm和3 μm的流感偶联物均诱导产生细胞因子的CD4 T细胞数量显著增加，并诱导促炎细胞因子IFNγ和TNFα的产生增加。相比之下，HBsAg与颗粒的偶联对T细胞反应没有显著影响。总之，抗原与500 nm和3 μm颗粒的偶联导致人Mo-DC对抗原的摄取增加，尽管这种偶联物诱导T细胞刺激的能力可能取决于PBMC供体的免疫状态。
