Institute of Pathogenic Biology, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control- Hengyang Medical School, University of South China, Hengyang, China.
Front Immunol. 2022 Nov 23;13:989620. doi: 10.3389/fimmu.2022.989620. eCollection 2022.
Considering the shortcomings in current chlamydia infection control strategies, a major challenge in curtailing infection is the implementation of an effective vaccine. The immune response induced by plasmid encoded Pgp3 was insufficient against infection, which requires adjuvant applications to achieve the robust immune response induced by Pgp3. There is increasing promising in developing adjuvant systems relying on the delivery potential of Pickering emulsions and the immunomodulatory effects of interleukin (IL)-12. Here, owing to the polycationic nature, chitosan particles tended to absorb on the oil/water interphase to prepare the optimized chitosan particle-stabilized Pickering emulsion (CSPE), which was designed as a delivery system for Pgp3 protein and IL-12. Our results showed that the average droplets size of CSPE was 789.47 ± 44.26 nm after a series of optimizations and about 90% antigens may be absorbed by CSPE owing to the positively charged surface (33.2 ± 3mV), and CSPE promoted FITC-BSA proteins uptake by macrophages. Furthermore, as demonstrated by Pgp3-specific antibody production and cytokine secretion, CSPE/IL-12 system enhanced significantly higher levels of Pgp3-specific IgG, IgG1, IgG2a, sIgA and significant cytokines secretion of IFN-γ, IL-2, TNF-α, IL-4. Similarly, vaginal chlamydial shedding and hydrosalpinx pathologies were markedly reduced in mice immunized with Pgp3/CSPE/IL-12. Collectively, vaccination with Pgp3/CSPE/IL-12 regimen elicited robust cellular and humoral immune response in mice resulting in an obvious reduction of live chlamydia load in the vaginal and inflammatory pathologies in the oviduct, which further propells the development of vaccines against infection.
鉴于当前衣原体感染控制策略的不足之处,遏制感染的主要挑战是实施有效的疫苗。质粒编码的 Pgp3 诱导的免疫应答不足以抵抗感染,这需要佐剂的应用来实现 Pgp3 诱导的强大免疫应答。越来越多的希望在于开发依赖于 Pickering 乳液的递药潜能和白细胞介素(IL)-12 的免疫调节作用的佐剂系统。在这里,由于壳聚糖颗粒带正电荷,因此趋向于吸附在油/水界面上,以制备优化的壳聚糖颗粒稳定的 Pickering 乳液(CSPE),该乳液被设计为 Pgp3 蛋白和 IL-12 的递药系统。我们的结果表明,经过一系列优化后,CSPE 的平均液滴尺寸为 789.47±44.26nm,由于带正电荷的表面(33.2±3mV),大约 90%的抗原可能被 CSPE 吸收,并且 CSPE 促进 FITC-BSA 蛋白被巨噬细胞摄取。此外,正如 Pgp3 特异性抗体产生和细胞因子分泌所证明的那样,CSPE/IL-12 系统显著增强了更高水平的 Pgp3 特异性 IgG、IgG1、IgG2a、sIgA 和 IFN-γ、IL-2、TNF-α、IL-4 的显著细胞因子分泌。同样,用 Pgp3/CSPE/IL-12 免疫的小鼠阴道衣原体脱落和输卵管积水病理明显减少。总之,用 Pgp3/CSPE/IL-12 方案免疫可在小鼠中引发强大的细胞和体液免疫应答,导致阴道中活衣原体负荷明显减少和输卵管中的炎症病理明显减少,这进一步推动了针对衣原体感染的疫苗的开发。