Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States.
Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, Michigan 48824, United States.
ACS Infect Dis. 2022 Mar 11;8(3):574-583. doi: 10.1021/acsinfecdis.1c00585. Epub 2022 Feb 16.
, a noninvasive mucosal pathogen, is endemic in more than 50 countries. Oral cholera vaccines, based on killed whole-cell strains of , can provide significant protection in adults and children for 2-5 years. However, they have relatively limited direct protection in young children. To overcome current challenges, in this study, a potential conjugate vaccine was developed by linking -specific polysaccharide (OSP) antigen purified from O1 El Tor Inaba strain PIC018 with Qβ virus-like particles efficiently via squarate chemistry. The Qβ-OSP conjugate was characterized with mass photometry (MP) on the whole particle level. Pertinent immunologic display of OSP was confirmed by immunoreactivity of the conjugate with convalescent phase samples from humans with cholera. Mouse immunization with the Qβ-OSP conjugate showed that the construct generated prominent and long-lasting IgG antibody responses against OSP, and the resulting antibodies could recognize the native lipopolysaccharide from O1 Inaba. This was the first time that Qβ was conjugated with a bacterial polysaccharide for vaccine development, broadening the scope of this powerful carrier.
霍乱弧菌是一种非侵袭性的黏膜病原体,在 50 多个国家流行。基于霍乱弧菌全细胞株的口服霍乱疫苗可为成人和儿童提供 2-5 年的显著保护,但对幼儿的直接保护作用相对有限。为了克服当前的挑战,在这项研究中,我们通过 squarate 化学方法将从 O1 型 El Tor Inaba 菌株 PIC018 中纯化的霍乱弧菌 O 特异性多糖(OSP)抗原与 Qβ病毒样颗粒有效连接,开发了一种潜在的结合疫苗。通过整颗粒水平的质量光度法(MP)对 Qβ-OSP 结合物进行了表征。结合物与霍乱恢复期患者的血清样本的免疫反应性证实了 OSP 的适当免疫展示。用 Qβ-OSP 结合物对小鼠进行免疫接种表明,该构建体针对 OSP 产生了显著且持久的 IgG 抗体反应,并且产生的抗体可以识别来自 O1 型 Inaba 的天然脂多糖。这是 Qβ首次与细菌多糖结合用于疫苗开发,拓宽了这种强大载体的应用范围。