Antibody avidity maturation as index for Immune resilience against SARS-CoV-2

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15927
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Osaka Metropolitan University
• Principal Investigator: Nakagama Yu 大阪公立大学, 大学院医学研究科, 准教授 (60846880)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: SARS-CoV-2 / 中和抗体 / 親和性成熟 / ワクチン / 自然感染

Outline of Final Research Achievements

Antibody maturation is important for viral neutralization, especially for broad neutralizing capacity, supporting the relevance of additional booster vaccination due to concerns about delayed avidity maturation in the vaccinees. In vitro evidence, showing strong association between SARS-CoV-2 high affinity antibodies and broad cross-neutralizability, clearly explains from the molecular perspective the lower number of real-world re-infections compared with the higher number of post-vaccination breakthrough infections. The findings altogether support adaptive decision making regarding vaccination strategies. The project further assessed the advantages of hybrid immunity, as well as the adaptive immunity development in vulnerable populations including cancer patients, octogenarians, and immunocompromised patients, from the view point of antibody avidity maturation kinetics.

Free Research Field

感染症科学

Academic Significance and Societal Importance of the Research Achievements

抗体アビディティ成熟は、SARS-CoV-2中和能、特に中和能広域化に重要であることが示された。ワクチン接種においてはアビディティ成熟の遅延が懸念されるため、追加ブースター接種の妥当性が支持された。SARS-CoV-2感染回復者が持つ高親和性抗体が、変異株に対しても広域な交差中和活性を発揮しうる、というin vitroのエビデンスは、リアルワールドにおいて回復者が再感染を起こす頻度が低いこと、ワクチン被接種者ブレイクスルー感染の頻度が多いことを、その分子背景から巧妙に説明した。本研究成果によって、ワクチン接種戦略に関するアクティブかつアダプティブな意思決定を支援するエビデンスが創出された。