Li Pei, Liu Qing, Luo Hongyan, Liang Kang, Han Yue, Roland Kenneth L, Curtiss Roy, Kong Qingke
1Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130 China.
2Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ 85287 USA.
NPJ Vaccines. 2018 Jan 9;3:1. doi: 10.1038/s41541-017-0041-5. eCollection 2018.
Typhi is the causative agent of typhoid fever in humans, responsible for approximately 21 million infections and 222,000 deaths globally each year. The current licensed vaccines provide moderate protection to recipients aged >2 years. Prior work on typhoid vaccines has focused on injectable Vi capsular polysaccharide or Vi-protein conjugates and live, oral attenuated . Typhi vaccines to induce humoral anti-Vi antibodies, while the value and importance of anti-O9 antibodies is less well established. In this study, we constructed a . Typhimurium strain that synthesizes Vi capsular antigen in vivo and produces the immunodominant O9-antigen polysaccharide instead of its native O4-antigen. The live recombinant attenuated . Typhimurium mutants were effective in stimulating anti-Vi and anti-O9 antibodies in a mouse model, and the surface Vi capsular expression did not affect the immune responses against the O9 O-antigen polysaccharide. Moreover, the resulting anti-Vi and anti-O9 antibodies were effective at killing . Typhi and other spp. expressing Vi or O9 antigen polysaccharides and provided efficient protection against lethal challenge by . Typhimurium and . Enteritidis. Our work highlights the strategy of developing live attenuated . Typhimurium vaccines to prevent typhoid fever by targeting the both Vi capsular and O9 O-polysaccharide antigens simultaneously.
伤寒杆菌是人类伤寒热的病原体，每年在全球导致约2100万例感染和22.2万人死亡。目前已获许可的疫苗对2岁以上的接种者提供中等程度的保护。先前关于伤寒疫苗的研究主要集中在注射用Vi荚膜多糖或Vi蛋白结合物以及口服减毒活疫苗。伤寒疫苗可诱导体液抗Vi抗体，而抗O9抗体的价值和重要性尚未得到充分证实。在本研究中，我们构建了一株鼠伤寒沙门氏菌菌株，该菌株在体内合成Vi荚膜抗原，并产生免疫显性的O9抗原多糖而非其天然的O4抗原。这种活的重组减毒鼠伤寒沙门氏菌突变体在小鼠模型中能有效刺激抗Vi和抗O9抗体，且表面Vi荚膜表达不影响针对O9 O抗原多糖的免疫反应。此外，产生的抗Vi和抗O9抗体能有效杀死表达Vi或O9抗原多糖的伤寒杆菌及其他菌种，并提供针对鼠伤寒沙门氏菌和肠炎沙门氏菌致死性攻击的有效保护。我们的工作突出了开发活减毒鼠伤寒沙门氏菌疫苗的策略，即通过同时靶向Vi荚膜和O9 O多糖抗原预防伤寒热。
