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自组装纳米颗粒血凝素流感疫苗可诱导高抗体应答。

Self-Assembling Nanoparticle Hemagglutinin Influenza Vaccines Induce High Antibody Response.

机构信息

Department of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, China.

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Xianyang 712100, China.

出版信息

Int J Mol Sci. 2024 Jul 1;25(13):7259. doi: 10.3390/ijms25137259.

Abstract

As a highly pathogenic avian virus, H5 influenza poses a serious threat to livestock, the poultry industry, and public health security. Hemagglutinin (HA) is both the dominant epitope and the main target of influenza-neutralizing antibodies. Here, we designed a nanoparticle hemagglutinin influenza vaccine to improve the immunogenicity of the influenza vaccine. In this study, HA5 subtype influenza virus was used as the candidate antigen and was combined with the artificially designed double-branch scaffold protein I53_dn5 A and B. A structurally correct and bioactive trimer HA5-I53_dn5B/Y98F was obtained through secretion and purification using an insect baculovirus expression system; I53_dn5A was obtained by purification using a prokaryotic expression system. HA5-I53_dn5B/Y98F and I53_dn5A self-assembled into spherical nanoparticles (HA5-I53_dn5) in vitro with a diameter of about 45 nm. Immunization and serum test results showed that both HA5-I53_dn5B/Y98F and HA5-I53_dn5 could induce HA5-specific antibodies; however, the immunogenicity of HA5-I53_dn5 was better than that of HA5-I53_dn5B/Y98F. Groups treated with HA5-I53_dn5B and HA5-I53_dn5 nanoparticles produced IgG antibody titers that were not statistically different from those of the nanoparticle-containing adjuvant group. This production of trimerized HA5-I53_dn5B and HA5-I53_dn5 nanoparticles using baculovirus expression provides a reference for the development of novel, safe, and efficient influenza vaccines.

摘要

作为一种高致病性禽流感病毒,H5 流感对畜牧业、家禽业和公共卫生安全构成严重威胁。血凝素 (HA) 既是流感中和抗体的主要表位,也是主要靶标。在这里,我们设计了一种纳米颗粒血凝素流感疫苗,以提高流感疫苗的免疫原性。在这项研究中,使用 HA5 亚型流感病毒作为候选抗原,并将其与人工设计的双分支支架蛋白 I53_dn5 A 和 B 结合。通过使用昆虫杆状病毒表达系统进行分泌和纯化,获得了结构正确且具有生物活性的三聚体 HA5-I53_dn5B/Y98F;通过原核表达系统纯化获得 I53_dn5A。HA5-I53_dn5B/Y98F 和 I53_dn5A 在体外自组装成直径约为 45nm 的球形纳米颗粒(HA5-I53_dn5)。免疫和血清检测结果表明,HA5-I53_dn5B/Y98F 和 HA5-I53_dn5 均可诱导 HA5 特异性抗体;然而,HA5-I53_dn5 的免疫原性优于 HA5-I53_dn5B/Y98F。用 HA5-I53_dn5B 和 HA5-I53_dn5 纳米颗粒处理的组产生的 IgG 抗体滴度与含纳米颗粒佐剂组没有统计学差异。使用杆状病毒表达系统生产三聚化的 HA5-I53_dn5B 和 HA5-I53_dn5 纳米颗粒为新型、安全、有效的流感疫苗的开发提供了参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731e/11241447/f63a76048e19/ijms-25-07259-g001.jpg

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