Bonaiti Elena, Muraro Manuele G, Robert Philippe A, Jakscha Jens, Dirnhofer Stefan, Martin Ivan, Berger Christoph T
Translational Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.
Tissue Engineering, Department of Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland.
Front Immunol. 2024 Sep 17;15:1425455. doi: 10.3389/fimmu.2024.1425455. eCollection 2024.
Vaccination is one of the most effective infection prevention strategies. Viruses with high mutation rates -such as influenza- escape vaccine-induced immunity and represent significant challenges to vaccine design. Influenza vaccine strain selection is based on circulating strains and immunogenicity testing in animal models with limited predictive outcomes for vaccine effectiveness in humans.
We developed a human vaccination model using human tonsil tissue explants cultured in 3D perfusion bioreactors to be utilized as a platform to test and improve vaccines.
Tonsils cultured in bioreactors showed higher viability, metabolic activity, and more robust immune responses than those in static cultures. The vaccination system responded to various premanufactured vaccines, protein antigens, and antigen combinations. In particular, a multivalent immunization with three phylogenetically distant H3N2 influenza strains showed evidence for broader B cell activation and induced higher antibody cross-reactivity than combinations with more related strains. Moreover, we demonstrate the capacity of our model to generate de novo humoral immune responses to a model antigen.
Perfusion-cultured tonsil tissue may be a valuable human model for immunology research with potential application in vaccine candidate selection.
接种疫苗是最有效的感染预防策略之一。像流感这类具有高突变率的病毒会逃避疫苗诱导的免疫，给疫苗设计带来重大挑战。流感疫苗毒株的选择基于流行毒株以及在动物模型中的免疫原性测试，但其对人类疫苗有效性的预测结果有限。
我们利用在三维灌注生物反应器中培养的人扁桃体组织外植体开发了一种人体疫苗接种模型，将其用作测试和改进疫苗的平台。
与静态培养的扁桃体相比，在生物反应器中培养的扁桃体具有更高的活力、代谢活性和更强的免疫反应。该疫苗接种系统对各种预制疫苗、蛋白质抗原和抗原组合均有反应。特别是，用三种系统发育距离较远的H3N2流感毒株进行多价免疫显示，与亲缘关系更近的毒株组合相比，其能激活更广泛的B细胞，并诱导更高的抗体交叉反应性。此外，我们证明了我们的模型对模型抗原产生从头体液免疫反应的能力。
灌注培养的扁桃体组织可能是免疫研究中有价值的人体模型，在候选疫苗选择方面具有潜在应用价值。
