Abstract：
Coronavirus disease 2019 (COVID-19) has caused a global pandemic since its onset in 2019, and the development of effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to induce potent and long-lasting immunity remains a priority. Herein, we prepared two Lactobacillus exopolysaccharide (EPS) nanoparticle adjuvants (NPs 7-4 and NPs 8-2) that were constructed by using sulfation-modified EPS and quaternization-modified chitosan. These two NPs displayed a spherical morphology with sizes of 39 and 47 nm. Furthermore, the zeta potentials of NPs 7-4 and NPs 8-2 were 50.40 and 44.40 mV, respectively. In vitro assays demonstrated that NPs could effectively adsorb antigenic proteins and exhibited a sustained release effect. Mouse immunization tests showed that the NPs induced the expression of cytokines and chemokines at the injection site and promoted the uptake of antigenic proteins by macrophages. Mechanically, the NPs upregulated the expression of pattern recognition receptors (toll-like receptors and nod-like receptors) and activated the immune response of T cells and the production of neutralizing antibodies. In addition, the NP adjuvants had favorable immune-enhancing effects in cats, which are of great significance for controlling the trans-host transmission and re-endemicity of SARS-CoV-2. Overall, we demonstrated that NP-adjuvanted SARS-CoV-2 receptor binding domain proteins could induce robust specific humoral and cellular immunity.
摘要：
2019年冠状病毒病（COVID-19）自2019年爆发以来已引起全球大流行，开发有效的严重急性呼吸道综合症冠状病毒2（SARS-CoV-2）疫苗以诱导有效和持久的免疫力仍然是当务之急。在这里，我们制备了两种乳杆菌胞外多糖（EPS）纳米佐剂（NPs7-4和NPs8-2），它们是通过使用硫酸化改性的EPS和季铵化改性的壳聚糖构建的。这两个NP显示出尺寸为39和47nm的球形形态。此外，NPs7-4和NPs8-2的zeta电位分别为50.40和44.40mV，分别。体外实验表明，NP能有效吸附抗原蛋白，并表现出缓释作用。小鼠免疫试验表明，NPs在注射部位诱导细胞因子和趋化因子的表达，并促进巨噬细胞对抗原蛋白的摄取。机械上,NP上调模式识别受体（toll样受体和nod样受体）的表达，并激活T细胞的免疫反应和中和抗体的产生。此外,NP佐剂对猫有良好的免疫增强作用，这对于控制SARS-CoV-2的跨宿主传播和再流行具有重要意义。总的来说,我们证明了NP佐剂的SARS-CoV-2受体结合域蛋白可以诱导强大的特异性体液和细胞免疫。
