Comprehensive study on HIV-specific ADCC responses using library clinical isolates

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08458
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Shigeyoshi Harada 国立感染症研究所, エイズ研究センター, 主任研究官 (30508643)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: HIV / AIDS

Outline of Final Research Achievements

The main objective of this study was to comprehensively analyze ADCC activity in HIV-infected specimens as a basic research for a novel therapeutic strategy aimed at cure of HIV latently infected cells.
As a result, we succeeded in constructing a system for measuring ADCC activity and obtained basic data on the relationship between clinical course and ADCC activity, as well as the relationship between ADCC activity and reservoir size.
In addition, we developed the "expansion of the anti-HIV antibody enhancer library" for the purpose of enhancing ADCC activity, and succeeded in finding several categories of "anti-HIV antibody enhancers" and pharmacophores that differ not only in their chemical structural framework but also in their binding regions to target Envs. These are expected to contribute to the development of new therapeutic methods.

Free Research Field

HIV感染症

Academic Significance and Societal Importance of the Research Achievements

現行の抗HIV薬は治癒できないため、生涯服薬継続という最大課題を残す。他方、理論上では、有効なADCC抗体を誘導できる感染症例では、感染細胞排除が進み、レザボアサイズが縮小され、それに伴いウイルス抑制効果および抗ウイルス治療効果が向上する可能性が推察される。本研究により「ADCC活性測定系の最適化」、「抗HIV抗体増強剤ライブラリーの拡充」、および「臨床検体に対する各種解析」を進展することができ、臨床検体におけるADCC活性知見およびADCC活性を惹起させる新規治療法開発の基盤データを得ることができた。これらは新規治療法開発の一助となると考えられる。