State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Experimental Research, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou 510060, P. R. China.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361102, P. R. China.
Nano Lett. 2021 Mar 24;21(6):2476-2486. doi: 10.1021/acs.nanolett.0c04687. Epub 2021 Mar 8.
Epstein-Barr virus (EBV) infection is a global health concern infecting over 90% of the population. However, there is no currently available vaccine. EBV primarily infects B cells, where the major glycoprotein 350 (gp350) is the main target of neutralizing antibodies. Given the advancement of nanoparticle vaccines, we describe rationally designed vaccine modalities presenting 60 copies of gp350 on self-assembled nanoparticles in a repetitive array. In a mouse model, gp350s on lumazine synthase (LS) and I3-01 adjuvanted with MF59 or aluminum hydroxide (Alhydrogel) elicited over 65- to 133-fold higher neutralizing antibody titers than the corresponding gp350 monomer to EBV. Furthermore, immunization with gp350D-LS and gp350D-I3-01 vaccine induced a Th2-biased response. For the nonhuman primate model, gp350D-LS in MF59 elicited higher titers of total IgG and neutralizing antibodies than the monomeric gp350D. Overall, these results support gp350D-based nanoparticle vaccine design as a promising vaccine candidate for potent protection against EBV infection.
EB 病毒（EBV）感染是一个全球性的健康问题，感染了超过 90%的人口。然而，目前还没有可用的疫苗。EBV 主要感染 B 细胞，其中主要糖蛋白 350（gp350）是中和抗体的主要靶标。鉴于纳米颗粒疫苗的进步，我们描述了合理设计的疫苗模式，在重复排列的自组装纳米颗粒上呈现 60 个 gp350 拷贝。在小鼠模型中，与相应的 gp350 单体相比，亮氨酸合酶（LS）和 I3-01 佐剂的 MF59 或氢氧化铝（Alhydrogel）上的 gp350s 诱导的中和抗体滴度高出 65 至 133 倍。此外，用 gp350D-LS 和 gp350D-I3-01 疫苗免疫诱导了 Th2 偏向的反应。对于非人灵长类动物模型，MF59 中的 gp350D-LS 引起的总 IgG 和中和抗体滴度高于单体 gp350D。总的来说，这些结果支持基于 gp350D 的纳米颗粒疫苗设计作为一种有前途的疫苗候选物，能够有效预防 EBV 感染。
