Abstract：
Despite the great success of vaccines in various infectious diseases, most current vaccines are not effective enough, and on the contrary, clinically approved alum adjuvants cannot induce sufficient immune responses, including a potent cellular immune response to confer protection. In this study, we used Nanochelating Technology to develop novel nanoadjuvants to boost the potency of the alum-adjuvanted inactivated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine. BALB/c mice were immunized twice over 2 weeks with different doses of adjuvanted-vaccine formulations and immune responses were assessed. The analysis results of IFN-γ and IL-17 cytokines demonstrated the effectiveness of the nanoadjuvants produced by the Nanochelating Technology in shifting the alum-based vaccine toward a stronger Th1 pattern. In addition, these nanoadjuvants improved IL-2 cytokine response, which shows the efficacy of these novel formulations in inducing specific T lymphocyte proliferation. Using these nanoadjuvants increased IL-10 cytokine secretion that may be representative of a better immunoregulatory impact and may also potentially prevent immunopathology responses. Moreover, specific IgG titer analysis revealed the potency of these nanoadjuvants in improving humoral immune responses. The enzyme-linked immunosorbent assay of receptor-binding domain (RBD)-specific IgG response showed that the developed novel formulations induced strong IgG responses against this protein. This study shows that the nanostructures produced by the Advanced Nanochelating Technology have potent adjuvant effects on alum-based SARS-CoV-2 vaccines to not only compensate for alum weakness in inducing the cellular immune responses by smart regulation of the immune system but also significantly improve the humoral and cellular immune responses simultaneously.
摘要：
尽管疫苗在各种传染病中取得了巨大成功，目前大多数疫苗都不够有效，相反,临床批准的明矾佐剂不能诱导足够的免疫反应，包括有效的细胞免疫反应以赋予保护。在这项研究中,我们使用纳米凝胶技术来开发新的纳米佐剂，以提高含明矾佐剂的灭活严重急性呼吸综合征冠状病毒-2（SARS-CoV-2）疫苗的效力。在2周内用不同剂量的佐剂化疫苗制剂免疫BALB/c小鼠两次,并评估免疫应答。IFN-γ和IL-17细胞因子的分析结果证明了由Nanochelating技术产生的纳米佐剂在将基于明矾的疫苗向更强的Th1模式转变中的有效性。此外,这些纳米佐剂改善了IL-2细胞因子反应，其显示了这些新制剂在诱导特异性T淋巴细胞增殖中的功效。使用这些纳米佐剂增加IL-10细胞因子分泌,这可以代表更好的免疫调节作用,并且还可以潜在地防止免疫病理学应答。此外，特异性IgG滴度分析揭示了这些纳米佐剂在改善体液免疫应答中的效力.受体结合域（RBD）特异性IgG反应的酶联免疫吸附测定表明，开发的新型制剂可诱导针对该蛋白的强IgG反应。这项研究表明，先进的纳米石墨化技术产生的纳米结构对基于明矾的SARS-CoV-2疫苗具有有效的佐剂作用，不仅可以通过免疫系统的智能调节来补偿明矾在诱导细胞免疫应答方面的弱点，而且还可以同时显着改善体液和细胞免疫应答。
