Document Type

Article

Publication Date

2-17-2015

Publication Title

PloS One

Department

Thayer School of Engineering

Abstract

Design of an envelope-based immunogen capable of inducing a broadly neutralizing anti- body response is thought to be key to the development of a protective HIV-1 vaccine. How- ever, the broad diversity of viral variants and a limited ability to produce native envelope have hampered such design efforts. Here we describe adaptation of the yeast display sys- tem and use of a combinatorial protein engineering approach to permit directed evolution of HIV envelope variants. Because the intrinsic instability and complexity of this trimeric glyco- protein has greatly impeded the development of immunogens that properly represent the structure of native envelope, this platform addresses an essential need for methodologies with the capacity to rapidly engineer HIV spike proteins towards improved homogeneity, stability, and presentation of neutralizing epitopes. We report for the first time the display of a designed SOSIP gp140 on yeast, and the in vitro evolution of derivatives with greatly im- proved expression and binding to conformation-dependent antibodies. These efforts repre- sent an initial and critical step toward the ability to rapidly engineer HIV-1 envelope immunogens via directed evolution.

DOI

10.1371/journal.pone.0117227

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