作者
Kevin O Saunders, Kevin Wiehe, Ming Tian, Priyamvada Acharya, Todd Bradley, S Munir Alam, Eden P Go, Richard Scearce, Laura Sutherland, Rory Henderson, Allen L Hsu, Mario J Borgnia, Haiyan Chen, Xiaozhi Lu, Nelson R Wu, Brian Watts, Chuancang Jiang, David Easterhoff, Hwei-Ling Cheng, Kelly McGovern, Peyton Waddicor, Aimee Chapdelaine-Williams, Amanda Eaton, Jinsong Zhang, Wes Rountree, Laurent Verkoczy, Mark Tomai, Mark G Lewis, Heather R Desaire, Robert J Edwards, Derek W Cain, Mattia Bonsignori, David Montefiori, Frederick W Alt, Barton F Haynes
发表日期
2019/12/6
期刊
Science
卷号
366
期号
6470
页码范围
eaay7199
出版商
American Association for the Advancement of Science
简介
INTRODUCTION
A major goal of HIV-1 vaccine development is the design of immunogens that induce broadly neutralizing antibodies (bnAbs). However, vaccination of humans has not resulted in the induction of affinity-matured and potent HIV-1 bnAbs. To devise effective vaccine strategies, we previously determined the maturation pathway of select HIV-1 bnAbs from acute infection through neutralizing antibody development. During their evolution, bnAbs acquire an abundance of improbable amino acid substitutions as a result of nucleotide mutations at variable region sequences rarely targeted by activation-induced cytidine deaminase, the enzyme responsible for antibody mutation. A subset of improbable mutations is essential for broad neutralization activity, and their acquisition represents a key roadblock to bnAb development.
RATIONALE
Current bnAb lineage–based vaccine strategies can initiate bnAb …
学术搜索中的文章
KO Saunders, K Wiehe, M Tian, P Acharya, T Bradley… - Science, 2019