Studies on the structure and function of Pentamer, the cell tropism determinant of cytomegalovirus, and on its induction of protective immunity

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08815
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Virology
• Research Institution: Gifu Pharmaceutical University
• Principal Investigator: Inoue Naoki 岐阜薬科大学, 薬学部, 教授 (90183186)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: サイトメガロウイルス / 先天性感染 / ワクチン / 感染防御 / 細胞指向性 / ペンタマー / 動物モデル / 中和抗体

Outline of Final Research Achievements

As congenital cytomegalovirus (CMV) infection causes developmental abnormalities in children, the development of CMV vaccines is critical to public health. The pentameric complex of glycoproteins (Pentamer), which is required for human CMV infection of endothelial and epithelial cells, is considered to be a potent vaccine antigen. As guinea pig CMV (GPCMV) infects congenitally and encodes homologs of all Pentamer components, GPCMV models can be useful for the development of vaccine strategies. Here, using several GPCMV mutants with an alteration in GP131, we identified critical sequences for the structure and functions of Pentamer. We demonstrated that Pentamer but not gB induced a high level of neutralizing antibodies against GPCMV infection of macrophages and that immunization with Pentamer protected guinea pigs from GPCMV infection. Finally, we found that anti-Pentamer antibodies neutralized all clinical isolates irrespective of their polymorphisms in the genes encoding Pentamer.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

先天性サイトメガロウイルス(CMV)感染を防ぐためのワクチンの候補抗原であるペンタマーの細胞指向性に関わる構造と機能に関する詳細を明らかにするとともに、動物モデルにおいてペンタマーを免疫することで感染防御が可能であることを実証した。さらに、様々なヒトの臨床分離株の感染をペンタマーに対する抗体で中和できることを明らかにした。本研究は、CMVワクチンの開発の方向性を明確にする社会的意義を有する。