Antibody-mediated synergy and interference in the neutralization of SARS-CoV at an epitope cluster on the spike protein

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• 作者：Lilin Zhong ; Lia Haynes ; Evi Budo Struble ; Azaibi Tamin ; Maria Luisa Virata-Theimer ; Pei Zhang
• 关键词：SARS-CoV ; Monoclonal antibody ; Neutralization ; Epitope
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2009
• 出版时间：18 December 2009
• 年：2009
• 卷：390
• 期：3
• 页码：1056-1060
• 全文大小：412 K

文摘

Incomplete neutralization of virus, especially when it occurs in the presence of excess neutralizing antibody, represents a biological phenomenon that impacts greatly on antibody-mediated immune prophylaxis of viral infection and on successful vaccine design. To understand the mechanism by which a virus escapes from antibody-mediated neutralization, we have investigated the interactions of non-neutralizing and neutralizing antibodies at an epitope cluster on the spike protein of severe acute respiratory syndrome coronavirus (SARS-CoV). The epitope cluster was mapped at the C-terminus of the spike protein; it consists of structurally intertwined epitopes recognized by two neutralizing monoclonal antibodies (mAbs), 341C and 540C, and a non-neutralizing mAb, 240C. While mAb 341C binds to a mostly linear epitope composed of residues ⁵⁰⁷PAT⁵⁰⁹ and V³⁴⁹, mAb 240C binds to an epitope that partially overlaps the former by at least two residues (P⁵⁰⁷ and A⁵⁰⁸). The epitope corresponding to mAb 540C is a conformational one, involving residues L⁵⁰⁴ and N⁵⁰⁵. In neutralization assays, non-neutralizing 240C disrupted virus neutralization by mAb 341C and/or mAb 540C, whereas a combination of mAbs 341C and 540C blocked virus infectivity synergistically. These findings indicate that the epitope cluster on the spike protein may serve as an evolutionarily conserved platform at which a dynamic interplay between neutralizing and non-neutralizing antibodies occurs, thereby determining the outcome of SARS-CoV infection.