Immunization with a Self-Assembled Nanoparticle Vaccine Elicits Potent Neutralizing Antibody Responses against EBV Infection
Immunization with a Self-Assembled Nanoparticle Vaccine Elicits Potent Neutralizing Antibody Responses against EBV Infection
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使用自组装纳米颗粒疫苗进行免疫可引发针对 EBV 感染的有效中和抗体反应。
DOI：
10.1021/acs.nanolett.0c04687
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发表时间：
2021-03-08
期刊：
影响因子：
10.8
通讯作者：
Zeng, Mu-Sheng
中科院分区：
文献类型：
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作者：
Kang, Yin-Feng;Zhang, Xiao;Zeng, Mu-Sheng
EB病毒（EBV）感染是一个全球性的健康问题，感染超过90%的人口。然而，目前没有可用的疫苗。EBV主要感染B细胞，其中主要糖蛋白350（gp 350）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，在重复阵列中的自组装纳米颗粒上呈现60个gp 350拷贝。在小鼠模型中，用MF 59或氢氧化铝（Alhydrogel）佐剂化的鲁马嗪合酶（LS）和I3-01上的gp 350引起比相应的gp 350单体高65至133倍的针对EBV的中和抗体滴度。此外，用gp 350 D（123）LS和gp 350 D（123）-I3-01疫苗免疫诱导Th 2偏向性应答。对于非人灵长类动物模型，MF 59中的350 D（123）-LS比单体gp 350 D（123）引起更高滴度的总IgG和中和抗体。总之，这些结果支持基于gp 350 D（123）的纳米颗粒疫苗设计作为有效保护对抗EBV感染的有希望的疫苗候选物。
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(123 )LS and gp350D(123)-I3-01 vaccine induced a Th2-biased response. For the nonhuman primate model, 350D(123)-LS in MF59 elicited higher titers of total IgG and neutralizing antibodies than the monomeric gp350D(123). Overall, these results support gp350D(123)-based nanoparticle vaccine design as a promising vaccine candidate for potent protection against EBV infection.