Departments of Physiology and Microbiology & Immunology, Goodman Cancer Research Center, 3655 Promenade Sir William Osler, Montréal, Québec H3G 1Y6, Canada.
Medicago Inc., 1020 route de l'Église, suite 600, Québec, Québec G1V 3V9, Canada.
Vaccine. 2018 Dec 18;36(52):8028-8038. doi: 10.1016/j.vaccine.2018.10.099. Epub 2018 Nov 14.
Cell-mediated immunity is an important component of immediate and long-term anti-viral protection. Dendritic cells (DCs) are essential for the induction of cell-mediated immunity by instructing the activation and differentiation of antigen-specific T cell responses. Activated DCs that express co-stimulatory molecules and pro-inflammatory cytokines are necessary to promote the development of type 1 immune responses required for viral control. Here we report that plant-derived virus-like particles (VLPs) bearing influenza hemagglutinins (HA) directly stimulate mouse and human DCs. DCs exposed to H1- and, to a lesser extent, H5-VLPs in vitro rapidly express co-stimulatory molecules and produce pro-inflammatory cytokines including IL-12, IL-6 and TNFα. Furthermore, these VLPs support the activation and differentiation of antigen-specific T cell responses. Mechanistically, H1-VLPs stimulate the activation of kinases typically activated downstream of pattern recognition receptors including AKT, p38, and p42/44 ERK. In vivo, immunization with plant-derived VLPs induce the accumulation of both cDC1s and cDC2 in the draining lymph node and a corresponding increase in T and B cells. VLPs devoid of HA protein activate DCs, suggesting they are intrinsically immunostimulatory. Together, the results demonstrate that these candidate plant-derived VLP vaccines have an inherent and direct stimulatory effect on DCs and can enhance the ability of DCs to promote Type 1 immune responses.
细胞介导的免疫是即时和长期抗病毒保护的重要组成部分。树突状细胞 (DCs) 通过指导抗原特异性 T 细胞反应的激活和分化,对于诱导细胞介导的免疫至关重要。表达共刺激分子和促炎细胞因子的激活 DC 对于促进控制病毒所需的 1 型免疫反应的发展是必要的。在这里,我们报告了携带流感血凝素 (HA) 的植物来源病毒样颗粒 (VLPs) 可直接刺激小鼠和人类 DCs。体外暴露于 H1-和(在较小程度上)H5-VLPs 的 DCs 迅速表达共刺激分子并产生促炎细胞因子,包括 IL-12、IL-6 和 TNFα。此外,这些 VLPs 支持抗原特异性 T 细胞反应的激活和分化。从机制上讲,H1-VLPs 刺激通常在模式识别受体下游激活的激酶的激活,包括 AKT、p38 和 p42/44 ERK。在体内,用植物来源的 VLPs 免疫会导致引流淋巴结中 cDC1 和 cDC2 的积累,以及 T 和 B 细胞的相应增加。缺乏 HA 蛋白的 VLPs 激活 DCs,表明它们具有内在的免疫刺激性。总之,这些结果表明这些候选植物源性 VLP 疫苗对 DCs 具有固有和直接的刺激作用,并增强了 DCs 促进 1 型免疫反应的能力。
Eur J Clin Pharmacol. 2023-8
Vaccines (Basel). 2021-7-8
Vaccines (Basel). 2020-4-14