Modular assembly and immunological evaluation of a promising bioconjugate nanovaccine against Klebsiella pneumoniae O2 serotype.

IF 6.9 1区 医学 Q1 IMMUNOLOGY
Peng Sun, Chao Pan, Huifang Xu, Bo Liu, Jingqin Ye, Kangfeng Wang, Yan Zhang, Ting Li, Li Zhu, Yating Wang, Hengliang Wang, Jun Wu
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引用次数: 0

Abstract

The antimicrobial-resistant (AMR) Klebsiella pneumoniae (Kp) poses an enormous threat to human health, with O2 serotypes accounting for up to 35-59% of infections. Although the O-polysaccharide (OPS) of the Kp O2 serotype can be used as an antigen target for vaccine preparation, its simple structure (only galactose repeats) makes it difficult to generate effective antibody responses and protection. Here, we prepared a novel Kp O2 OPS bioconjugate nanovaccine using protein glycan coupling technology (PGCT) and a SpyCatcher/SpyTag (SC/ST) orthogonal assembly system. The hepatitis B virus core antigen (HBc), which can assemble into nanoparticles, was used as a carrier to display OPS on its surface, allowing the bioconjugate to reach the nanoscale. The HBc-OPS exhibited attractive stability without aggregation or degradation for up to 10 months. A series of mouse experiments revealed the OPS-specific antibody activation ability of HBc-OPS and its protective effect against different infection doses. In particular, when coadministered with the AS03 adjuvant, all the mice were protected from higher doses of lethal attacks. Through in vitro and in vivo experiments, we found that the addition of AS03 further promoted the humoral immune response by stimulating increased levels of cytokines and T follicular helper (Tfh), germinal center B (GC B), and antigen-specific memory B cells. Moreover, we found that the use of AS03 as an adjuvant can provide a better protective effect than commonly used CpG-based adjuvants. Therefore, we have developed an attractive, stable, and effective bioconjugate nanovaccine against the Klebsiella pneumoniae O2 serotype. This bioconjugate nanovaccine design greatly potentiated the immunogenicity of polysaccharides, and the orthogonal modular assembly strategy reduced the technical difficulty of bioconjugate nanovaccine preparation, both of which could be applicable to the development of OPS conjugate vaccines for serotypes with low immunogenicity.

抗肺炎克雷伯菌O2血清型生物偶联纳米疫苗的模块化组装和免疫学评价
抗微生物药物耐药性肺炎克雷伯菌(Kp)对人类健康构成巨大威胁,O2血清型占感染总数的35%至59%。虽然Kp O2血清型的o -多糖(OPS)可以作为疫苗制备的抗原靶点,但其结构简单(只有半乳糖重复序列),难以产生有效的抗体应答和保护。本研究利用蛋白聚糖偶联技术(PGCT)和SpyCatcher/SpyTag (SC/ST)正交组装体系制备了一种新型Kp O2 OPS生物偶联纳米疫苗。乙型肝炎病毒核心抗原(HBc)可以组装成纳米颗粒,作为载体在其表面显示OPS,使生物偶联物达到纳米级。HBc-OPS表现出极好的稳定性,在长达10个月的时间里没有聚集或降解。一系列小鼠实验揭示了HBc-OPS的特异性抗体激活能力及其对不同感染剂量的保护作用。特别是,当与AS03佐剂共同施用时,所有小鼠都免受更高剂量的致命攻击。通过体外和体内实验,我们发现AS03的加入通过刺激细胞因子和T滤泡辅助细胞(Tfh)、生发中心B (GC B)和抗原特异性记忆B细胞水平的增加,进一步促进了体液免疫反应。此外,我们发现使用AS03作为佐剂可以提供比常用的基于cpg的佐剂更好的保护效果。因此,我们开发了一种有吸引力的、稳定的、有效的抗肺炎克雷伯菌O2血清型的生物偶联纳米疫苗。该生物偶联纳米疫苗设计大大增强了多糖的免疫原性,正交模块化组装策略降低了生物偶联纳米疫苗制备的技术难度,可用于低免疫原性血清型OPS结合疫苗的开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
NPJ Vaccines
NPJ Vaccines Immunology and Microbiology-Immunology
CiteScore
11.90
自引率
4.30%
发文量
146
审稿时长
11 weeks
期刊介绍: Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.
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