- 作者: Hsiao-Ling Chiang, Kang-Hao Liang, Ruei-Min Lu, Ting-Wen Kuo, Yi‑Ling Lin & Han-Chung Wu
- 作者服務機構: 1.Biomedical Translation Research Center (BioTReC), Academia Sinica, Taipei, Taiwan 2.Institute of Biomedical Sciences (IBMS), Academia Sinica, Taipei, Taiwan 3.Institute of Cellular and Organismic Biology (ICOB), Academia Sinica, No. 128, Academia Road, Section 2, Nankang, Taipei, 11529, Taiwan
- 中文摘要:
- 英文摘要:
Background
The COVID-19 pandemic continues to pose a significant worldwide threat to human health, as emerging SARS-CoV-2 Omicron variants exhibit resistance to therapeutic antibodies and the ability to evade vaccination-induced antibodies. Here, we aimed to identify human antibodies (hAbs) from convalescent patients that are potent and broadly neutralizing toward Omicron sublineages.
Methods
Using a single B-cell cloning approach, we isolated BA.5 specific human antibodies. We further examined the neutralizing activities of the most promising neutralizing hAbs toward different variants of concern (VOCs) with pseudotyped virus.
Results
Sixteen hAbs showed strong neutralizing activities against Omicron BA.5 with low IC50 values (IC50 < 20 ng/mL). Among four of the most promising neutralizing hAbs (RBD-hAb-B22, -B23, -B25 and -B34), RBD-hAb-B22 exhibited the most potent and broad neutralization profiles across Omicron subvariant pseudoviruses, with low IC50 values (7.7–41.6 ng/mL) and a low PRNT50 value (3.8 ng/mL) in plaque assays with authentic BA.5. It also showed potent therapeutic effects in BA.5-infected K18-hACE2 mice.
Conclusions
Thus, our efficient screening of BA.5-specific neutralizing hAbs from breakthrough infectious convalescent donors successfully yielded hAbs with potent therapeutic potential against multiple SARS-CoV-2 variants. - 中文關鍵字:
- 英文關鍵字: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Omicron, XBB.1.5, BQ.1.1, Single B cell cloning, Neutralizing human antibody