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J Biomed Sci . Broadly neutralizing human antibodies against Omicron subvariants of SARS-CoV-2

tetano

Editor, Senior Moderator
J Biomed Sci


. 2023 Jul 31;30(1):59.
doi: 10.1186/s12929-023-00955-x. Broadly neutralizing human antibodies against Omicron subvariants of SARS-CoV-2

Hsiao-Ling Chiang[SUP] 1 [/SUP], Kang-Hao Liang[SUP] 1 [/SUP], Ruei-Min Lu[SUP] 1 [/SUP], Ting-Wen Kuo[SUP] 1 [/SUP], Yi-Ling Lin[SUP] 1 2 [/SUP], Han-Chung Wu[SUP] 3 4 [/SUP]



Affiliations
Abstract

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 IC[SUB]50[/SUB] values (IC[SUB]50[/SUB] < 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 IC[SUB]50[/SUB] values (7.7-41.6 ng/mL) and a low PRNT[SUB]50[/SUB] 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.

Keywords: BQ.1.1; Neutralizing human antibody; Omicron; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); Single B cell cloning; XBB.1.5.

 
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