[저자] Lingshu Wang, Tongqing Zhou, Yi Zhang, Eun Sung Yang, Chaim A Schramm, Wei Shi, Amarendra Pegu, Olamide K Oloniniyi, Amy R Henry, Samuel Darko, Sandeep R Narpala, Christian Hatcher, David R Martinez, Yaroslav Tsybovsky, Emily Phung, Olubukola M Abiona, Avan Antia, Evan M Cale, Lauren A Chang, Misook Choe, Kizzmekia S Corbett, Rachel L Davis, Anthony T DiPiazza, Ingelise J Gordon, Sabrina Helmold Hait, Tandile Hermanus, Prudence Kgagudi, Farida Laboune, Kwanyee Leung, Tracy Liu, Rosemarie D Mason, Alexandra F Nazzari, Laura Novik, Sarah O'Connell, Sijy O'Dell, Adam S Olia, Stephen D Schmidt, Tyler Stephens, Christopher D Stringham, Chloe Adrienna Talana, I-Ting Teng, Danielle A Wagner, Alicia T Widge, Baoshan Zhang, Mario Roederer, Julie E Ledgerwood, Tracy J Ruckwardt, Martin R Gaudinski, Penny L Moore, Nicole A Doria-Rose, Ralph S Baric, Barney S Graham, Adrian B McDermott, Daniel C Douek, Peter D Kwong, John R Mascola, Nancy J Sullivan, John Misasi
[Category] MERS, SARS, 변종, 진단,
[Article Type] Article
[Source] PMC
Abstract
The emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identified four receptor binding domain-targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 23 variants, including the B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, and B.1.617 VOCs. Two antibodies are ultrapotent, with subnanomolar neutralization titers [half-maximal inhibitory concentration (IC 50 ) 0.3 to 11.1 nanograms per milliliter; IC 80 1.5 to 34.5 nanograms per milliliter). We define the structural and functional determinants of binding for all four VOC-targeting antibodies and show that combinations of two antibodies decrease the in vitro generation of escape mutants, suggesting their potential in mitigating resistance development.
All Keywords
【초록키워드】 antibodies, antibody, B.1.351, SARS-CoV-2 variant, in vitro, variants, Neutralizing activity, B.1.1.7, P.1, B.1.617, therapeutic, VOCs, B.1.429, B.1.526, convalescent, Donor, binding, escape mutants, Combination, Receptor binding, therapeutic antibodies, determinant, combinations, inhibitory concentration, neutralization titer, milliliter, decrease, reactive, highlight, functional, 【제목키워드】 antibody, SARS-CoV-2 variant,
{{{ 추상적인 }}}
치료 항체에 내성이 있는 전염성이 높은 SARS-CoV-2 변이체(VOC)의 출현은 광범위하게 반응성인 항체의 지속적인 발견에 대한 필요성을 강조합니다. 우리는 B.1.1.7, B.1.351, P.1, B.1.429, B.1.526 및 B를 포함한 23개의 변이체에 대해 강력한 중화 활성을 가진 3명의 조기 발병 회복기 기증자로부터 4개의 수용체 결합 도메인 표적화 항체를 확인했습니다. .1.617 VOC. 2개의 항체는 나노몰 이하 중화 역가로 초강력합니다[절반-최대 억제 농도(IC 50 ) 0.3~11.1나노그램/밀리리터; IC 80 밀리리터당 1.5~34.5나노그램). 우리는 4가지 VOC 표적 항체 모두에 대한 결합의 구조적 및 기능적 결정인자를 정의하고 두 항체의 조합이 시험관 내 탈출 돌연변이 생성을 감소시키는 것으로 나타났으며, 이는 내성 발달을 완화하는 잠재력을 시사합니다.