Li Ping, Yu Zihang, Jiang Ziyi, Jiang Yike, Shi Jingjing, Han Sanyang, Ma Lan
Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen 518132, China.
Vaccines (Basel). 2025 Mar 28;13(4):360. doi: 10.3390/vaccines13040360.
Epstein-Barr virus (EBV) infects approximately 95% of the global population, causing numerous malignancy-related cases annually and some autoimmune diseases. EBV-encoded gp350, gH, gL, gp42 and gB glycoproteins are identified as antigen candidates for their key role in viral entry, and nanoparticle vaccines displaying them were developed for the advantage of inducing cross-reactive B cell responses. : To develop liposomes displaying nanoparticle vaccine, we synthesized liposomes to present the well-identified EBV-encoded gp350D glycoprotein on their surface to imitate the viral structure, through the conjugation between N-hydroxysuccinimide (NHS) groups on the liposomes and primary amine of antigens to form stable amide bond. Then we assessed the immunogenicity of the biomimetic Lipo-gp350D nanoparticle vaccine in Balb/c mice immunized experiments. : The results showed that the sera samples from Lipo-gp350D nanoparticle vaccine immunized mice collected at weeks 8, 10 and 12 had higher titers of gp350D protein-specific antibodies, compared to monomer gp350D protein control, and higher titers of neutralizing antibodies to block EBV-GFP infection in AKATA cells. Meanwhile, the Lipo-gp350D nanoparticle vaccine also induced higher percentage of CD8+ IFN-γ+ T cells in the spleen, but without significance in CD4+ IFN-γ+ T cells, and these isolated splenocytes showed a higher level of secreted IFN-γ. Moreover, no significant histopathological changes were observed in all vaccinated mice. : Altogether these data demonstrated that the liposome displaying promoted the immunogenicity of antigens, and the Lipo-gp350D nanoparticle vaccine candidate had potential application in blocking EBV infection. The liposome nanoparticle was a useful vector for antigen displaying to elicit effective immunity.
爱泼斯坦-巴尔病毒（EBV）感染了全球约95%的人口，每年导致大量与恶性肿瘤相关的病例以及一些自身免疫性疾病。EBV编码的gp350、gH、gL、gp42和gB糖蛋白因其在病毒进入过程中的关键作用而被确定为抗原候选物，展示这些糖蛋白的纳米颗粒疫苗因能诱导交叉反应性B细胞反应的优势而被开发出来。为了开发展示纳米颗粒疫苗的脂质体，我们合成了脂质体，通过脂质体上的N-羟基琥珀酰亚胺（NHS）基团与抗原的伯胺之间的共轭反应，在其表面呈现出已被充分鉴定的EBV编码的gp350D糖蛋白，以模仿病毒结构，从而形成稳定的酰胺键。然后我们在Balb/c小鼠免疫实验中评估了仿生Lipo-gp350D纳米颗粒疫苗的免疫原性。结果显示，与单体gp350D蛋白对照相比，在第8、10和12周收集的来自Lipo-gp350D纳米颗粒疫苗免疫小鼠的血清样本中，gp350D蛋白特异性抗体的滴度更高，并且对AKATA细胞中EBV-GFP感染的中和抗体滴度也更高。同时，Lipo-gp350D纳米颗粒疫苗还诱导脾脏中CD8+ IFN-γ+ T细胞的百分比更高，但在CD4+ IFN-γ+ T细胞中无显著差异，并且这些分离的脾细胞分泌的IFN-γ水平更高。此外，在所有接种疫苗的小鼠中未观察到明显的组织病理学变化。总之，这些数据表明展示抗原的脂质体促进了抗原的免疫原性，并且候选的Lipo-gp350D纳米颗粒疫苗在阻断EBV感染方面具有潜在应用。脂质体纳米颗粒是一种用于展示抗原以引发有效免疫的有用载体。
