Abstract：
Vibrio cholerae, a noninvasive mucosal pathogen, is endemic in more than 50 countries. Oral cholera vaccines, based on killed whole-cell strains of Vibrio cholerae, 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 O-specific polysaccharide (OSP) antigen purified from V. cholerae 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 Vibrio cholerae 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.
摘要：
霍乱弧菌,一种非侵入性粘膜病原体，在50多个国家流行。口服霍乱疫苗，基于被杀死的霍乱弧菌全细胞菌株，可以在成人和儿童中提供2-5年的显着保护。然而,他们对幼儿的直接保护相对有限。为了克服当前的挑战，在这项研究中，通过方格化学将从霍乱弧菌O1ElTorInaba菌株PIC018中纯化的O特异性多糖（OSP）抗原与Qβ病毒样颗粒有效地连接，开发了一种潜在的结合疫苗。用质量光度法(MP)在整个颗粒水平上表征Qβ-OSP缀合物。通过缀合物与来自患有霍乱的人的恢复期样品的免疫反应性来证实OSP的相关免疫学展示。用Qβ-OSP缀合物免疫小鼠表明构建体产生了针对OSP的显著且持久的IgG抗体应答,得到的抗体可以识别霍乱弧菌O1Inaba的天然脂多糖。这是首次将Qβ与细菌多糖结合用于疫苗开发，扩大这个强大载体的范围。
