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Total Synthesis and Immunological Evaluation of the Tri-d-glycero-d-manno-heptose Antigen of the Lipopolysaccharide as a Vaccine Candidate against Helicobacter pylori
Organic Letters ( IF 5.2 ) Pub Date : 2020-10-29 , DOI: 10.1021/acs.orglett.0c03105
Junchang Wang 1 , Yiyue Zhang 1 , Yirong Zhu 1 , Junru Liu 1 , Yan Chen 1 , Xin Cao 2 , You Yang 1
Affiliation  

Helicobacter pylori, the most common cause of chronic gastritis, peptic ulcers, and gastric cancers, infects around half of the world’s population. Although the drawbacks of antibiotic-based combination therapy are emerging, no effective vaccine is available to prevent H. pylori infections. Here, we describe the total synthesis of the unique α-(1→3)-linked tri-d-glycero-d-manno-heptose antigen from the lipopolysaccharide of H. pylori serogroups O3 and O6 and strains MO19, D2, D4, and D5 based on de novo synthesis of the differentially protected d-glycero-d-manno-heptosyl building blocks. Immunization of mice with the semisynthetic glycoconjugate elicited a very robust T-cell-dependent antigen-specific immune response, resulting in very high titers of IgG1 and IgG2b protective antibody isotypes. The postimmune sera recognized H. pylori NCTC 11637 and bound strongly to the surface of the intact bacteria.

中文翻译:

脂多糖的 Tri-d-glycero-d-manno-heptose 抗原作为抗幽门螺杆菌候选疫苗的全合成和免疫学评价

幽门螺杆菌是慢性胃炎、消化性溃疡和胃癌的最常见原因,感染了世界上大约一半的人口。尽管基于抗生素的联合疗法的缺点正在显现,但没有有效的疫苗可用于预防幽门螺杆菌感染。在这里,我们描述了独特的α-(1→3) -连接的三-的全合成d -甘油基- d -甘露-heptose抗原从脂多糖幽门螺杆菌血清群O3和O6和菌株MO19,D2,D4,和 D5 基于差异保护的d -甘油- d - 的从头合成甘露糖-糖基积木。用半合成糖缀合物对小鼠进行免疫接种引发了非常强大的 T 细胞依赖性抗原特异性免疫反应,导致 IgG1 和 IgG2b 保护性抗体同种型的滴度非常高。免疫后血清识别幽门螺杆菌NCTC 11637 并与完整细菌的表面强烈结合。
更新日期:2020-11-21
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