A built-in adjuvant-engineered mucosal vaccine against dysbiotic periodontal diseases.,Mucosal Immunology

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A built-in adjuvant-engineered mucosal vaccine against dysbiotic periodontal diseases.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2018-Nov-28 , DOI: 10.1038/s41385-018-0104-6
Sao Puth _{1,

2} , Seol Hee Hong _{1,

3} , Hee Sam Na ₄ , Hye Hwa Lee _{1,

2} , Youn Suhk Lee _{1,

3} , Soo Young Kim _{1,

2} , Wenzhi Tan _{1,

2} , Hye Suk Hwang _{1,

2} , Sethupathy Sivasamy _{1,

2} , Kwangjoon Jeong _{1,

2} , Joong-Ki Kook ₅ , Sug-Joon Ahn ₆ , In-Chol Kang ₇ , Je-Hwang Ryu ₃ , Jeong Tae Koh ₃ , Joon Haeng Rhee _{1,

2} , Shee Eun Lee _{1,

3}

Affiliation

Periodontitis is associated with a dysbiotic shift in the oral microbiome. Vaccine approaches to prevent microbial shifts from healthy to diseased state in oral biofilms would provide a fundamental therapeutic strategy against periodontitis. Since dental plaque formation is a polymicrobial and multilayered process, vaccines targeting single bacterial species would have limited efficacy in clinical applications. In this study, we developed a divalent mucosal vaccine consisting of a mixture of FlaB-tFomA and Hgp44-FlaB fusion proteins targeting virulence factors of inflammophilic bacteria Fusobacterium nucleatum and Porphyromonas gingivalis, respectively. Introduction of peptide linkers between FlaB and antigen improved the stability and immunogenicity of engineered vaccine antigens. The intranasal immunization of divalent vaccine induced protective immune responses inhibiting alveolar bone loss elicited by F. nucleatum and P. gingivalis infection. The built-in flagellin adjuvant fused to protective antigens enhanced antigen-specific antibody responses and class switch recombination. The divalent vaccine antisera recognized natural forms of surface antigens and reacted with diverse clinical isolates of Fusobacterium subspecies and P. gingivalis. The antisera inhibited F. nucleatum-mediated biofilm formation, co-aggregation of P. gingivalis and Treponema denticola, and P. gingivalis-host cell interactions. Taken together, the built-in adjuvant-engineered mucosal vaccine provides a technological platform for multivalent periodontitis vaccines targeting dysbiotic microbiome.

中文翻译：

一种针对生态失调牙周病的内置佐剂工程粘膜疫苗。

牙周炎与口腔微生物群的生态失调有关。预防口腔生物膜中微生物从健康状态转变为患病状态的疫苗方法将提供针对牙周炎的基本治疗策略。由于牙菌斑的形成是一个多微生物和多层过程，因此针对单一细菌种类的疫苗在临床应用中的功效有限。在这项研究中，我们开发了一种二价粘膜疫苗，由 FlaB-tFomA 和 Hgp44-FlaB 融合蛋白的混合物组成，分别针对嗜炎细菌核梭杆菌和牙龈卟啉单胞菌的毒力因子。在 FlaB 和抗原之间引入肽接头提高了工程疫苗抗原的稳定性和免疫原性。二价疫苗的鼻内免疫诱导了保护性免疫反应，抑制了具核梭杆菌和牙龈卟啉单胞菌感染引起的牙槽骨丢失。与保护性抗原融合的内置鞭毛蛋白佐剂增强了抗原特异性抗体反应和类别转换重组。二价疫苗抗血清识别表面抗原的天然形式，并与梭杆菌亚种和牙龈卟啉单胞菌的多种临床分离株发生反应。抗血清抑制具核梭杆菌介导的生物膜形成、牙龈卟啉单胞菌和牙龈密螺旋体的共聚集，以及牙龈卟啉单胞菌与宿主细胞的相互作用。总之，内置的佐剂工程粘膜疫苗为针对失调微生物组的多价牙周炎疫苗提供了技术平台。

更新日期：2019-01-26

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