Tryptophan 375 stabilizes the outer-domain core of gp120 for HIV vaccine immunogen design

Authors

• Duoyi Hu, University of Nebraska-Lincoln
• Dane Bowder, University of Nebraska-LincolnFollow
• Wenzhong Wei, University of Nebraska-Lincoln
• Jesse Thompson, University of Nebraska-LincolnFollow
• Mark A. Wilson, University of Nebraska-LincolnFollow
• Shi-Hua Xiang, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

2017

Citation

Vaccine 35 (2017) 3067–3075. doi:10.1016/j.vaccine.2017.04.054

Comments

Copyright (c) 2017 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license

Abstract

The outer-domain core of gp120 may serve as a better HIV vaccine immunogen than the full-length gp120 because of its greater stability and immunogenicity. In our previous report, we introduced two disulfide bonds to the outer-domain core of gp120 to fix its conformation into a CD4-bound state, which resulted in a significant increase in its immunogenicity when compared to the wild-type outer-domain core. In this report, to further improve the immunogenicity of the outer-domain core based immunogen, we have introduced a Tryptophan residue at gp120 amino acid sequence position 375 (375S/W). Our data from immunized guinea pigs indeed shows a striking increase in the immune response due to this stabilized core outer-domain. Therefore, we conclude that the addition of 375W to the outer-domain core of gp120 further stabilizes the structure of immunogen and increases the immunogenicity