National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 35053, Taiwan.
Graduate Institute of Immunology, China Medical University, Taichung 40402, Taiwan.
Sci Rep. 2016 Nov 9;6:36732. doi: 10.1038/srep36732.
This study describes the feasibility and adjuvant mechanism of a degradable emulsion for tuning adaptive immune responses to a vaccine antigen. We featured a mouse model with ovalbumin (OVA) as the antigen to deepen our understanding of the properties of a degradable emulsion-based adjuvant, dubbed PELC, interacting with immune cells and to elucidate their roles in vaccine immunogenicity in vivo. First, we demonstrated that the emulsion, which is stabilized by an amphiphilic bioresorbable polymer, shows degradation in mimic human body conditions and considerable tolerance in vivo. Then, we confirmed the model protein could be loaded into the emulsion and released from the matrix in a sustained manner, subsequently driving the production of antigen-specific antibodies. We also comprehended that PELC not only recruits antigen-presenting cells (APCs) to the injection site but also induces the activation of the recruited APCs and migration to the draining lymph nodes. As an adjuvant for cancer immunotherapy, PELC-formulated OVA could strongly enhance antigen-specific T-cell responses as well as anti-tumor ability with respected to non-formulated OVA, using OVA protein/EG7 cells as a tumor antigen/tumor cell model. Accordingly, our data paved the way for the clinical application of degradable emulsions based on amphiphilic bioresorbable polymers as vaccine adjuvants.
本研究描述了一种可降解乳剂在调节疫苗抗原适应性免疫反应中的可行性和辅助机制。我们以卵清蛋白(OVA)为抗原建立了一个小鼠模型,以深入了解一种名为 PELC 的可降解乳剂佐剂与免疫细胞相互作用的特性,并阐明其在体内疫苗免疫原性中的作用。首先,我们证明了由两亲性可生物降解聚合物稳定的乳剂在模拟人体条件下会发生降解,并且在体内具有相当的耐受性。然后,我们证实模型蛋白可以被加载到乳剂中并从基质中持续释放,从而驱动抗原特异性抗体的产生。我们还了解到,PELC 不仅可以招募抗原呈递细胞(APCs)到注射部位,还可以诱导募集的 APC 活化和向引流淋巴结迁移。作为癌症免疫治疗的佐剂,PELC 制剂的 OVA 能够强烈增强抗原特异性 T 细胞反应以及抗肿瘤能力,与未制剂的 OVA 相比,以 OVA 蛋白/EG7 细胞作为肿瘤抗原/肿瘤细胞模型。因此,我们的数据为基于两亲性可生物降解聚合物的可降解乳剂作为疫苗佐剂的临床应用铺平了道路。