Institute of Veterinary Immunology & Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing, China.
National Research Center of Engineering and Technology for Veterinary Biologicals, Jiangsu Academy of Agricultural Sciences, Nanjing, China.
Front Immunol. 2021 Nov 18;12:697292. doi: 10.3389/fimmu.2021.697292. eCollection 2021.
Ideally, a vaccine should provide life-long protection following a single administered dose. In our previous study, the immunopotentiator CVC1302, which contains pattern- recognition receptor (PRR) agonists, was demonstrated to prolong the lifetime of the humoral immune response induced by killed foot-and-mouth disease virus (FMDV) vaccine. To elucidate the mechanism by which CVC1302 induces long-term humoral immunity, we used 4-hydroxy-3-nitrophenylacetyl (NP)-OVA as a pattern antigen and administered it to mice along with CVC1302, emulsified together with Marcol 52 mineral oil (NP-CVC1302). From the results of NP-specific antibody levels, we found that CVC1302 could induce not only higher levels of NP-specific antibodies but also high-affinity NP-specific antibody levels. To detect the resulting NP-specific immune cells, samples were taken from the injection sites, draining lymph nodes (LNs), and bone marrow of mice injected with NP-CVC1302. The results of these experiments show that, compared with mice injected with NP alone, those injected with NP-CVC1302 had higher percentages of NP+ antigen-presenting cells (APCs) at the injection sites and draining LNs, higher percentages of follicular helper T cells (TFH), germinal center (GC) B cells, and NP+ plasma-blasts in the draining LNs, as well as higher percentages of NP+ long-lived plasma cells (LLPCs) in the bone marrow. Additionally, we observed that the inclusion of CVC1302 in the immunization prolonged the lifetime of LLPCs in the bone marrow by improving the transcription expression of anti-apoptotic transcription factors such as Mcl-1, Bcl-2, BAFF, BCMA, Bax, and IRF-4. This research provides a blueprint for designing new generations of immunopotentiators.
理想情况下，疫苗在单次给药后应提供终身保护。在我们之前的研究中，含有模式识别受体 (PRR) 激动剂的免疫增强剂 CVC1302 被证明可以延长灭活口蹄疫病毒 (FMDV) 疫苗诱导的体液免疫反应的寿命。为了阐明 CVC1302 诱导长期体液免疫的机制，我们使用 4-羟基-3-硝基苯乙酰基 (NP)-OVA 作为模式抗原，并与 CVC1302 一起给予小鼠，与 Marcol 52 矿物油 (NP-CVC1302) 乳化。从 NP 特异性抗体水平的结果来看，我们发现 CVC1302 不仅可以诱导更高水平的 NP 特异性抗体，还可以诱导高亲和力的 NP 特异性抗体水平。为了检测由此产生的 NP 特异性免疫细胞，从注射 NP-CVC1302 的小鼠的注射部位、引流淋巴结 (LN) 和骨髓中采集样本。这些实验的结果表明，与单独注射 NP 的小鼠相比，注射 NP-CVC1302 的小鼠在注射部位和引流 LN 中具有更高百分比的 NP+抗原呈递细胞 (APC)，在引流 LN 中具有更高百分比的滤泡辅助 T 细胞 (TFH)、生发中心 (GC) B 细胞和 NP+浆母细胞，以及骨髓中具有更高百分比的 NP+长寿浆细胞 (LLPC)。此外，我们观察到 CVC1302 的包含在免疫接种中通过改善抗凋亡转录因子如 Mcl-1、Bcl-2、BAFF、BCMA、Bax 和 IRF-4 的转录表达来延长骨髓中 LLPC 的寿命。这项研究为设计新一代免疫增强剂提供了蓝图。
