Designed recombinant adenovirus type 5 vector induced envelope-specific CD8+ cytotoxic T lymphocytes and cross-reactive neutralizing antibodies against human immunodeficiency virus type 1

✍ Scribed by Takehiro Ura; Atsushi Yoshida; Ke-Qin Xin; Shinji Yoshizaki; Sayaka Yashima; Shinya Abe; Hiroyuki Mizuguchi; Kenji Okuda

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 347 KB
• Volume: 11
• Category: Article
• ISSN: 1099-498X
• DOI: 10.1002/jgm.1277

✦ Synopsis

Abstract

Background

A monoclonal antibody (mAb) 2F5 binds to the membrane‐proximal external region (MPER) of the transmembrane subunit gp41 of human immunodeficiency virus type 1 (HIV‐1) is known to broadly neutralize HIV‐1 strains. The Adenovirus type 5 vector (Ad5) has been widely applied for HIV‐1 vaccine, and hexon hypervariable region 5 (HVR5) is exposed on viral surface and easily target host immune responses against Ad5.

Methods

We constructed a recombinant adenovirus type 5 vector (rAd5) with a 2F5‐binding epitope (ELDKWA) of MPER on Ad5‐HVR5. In addition, we developed rAd5 encoding the HIV‐1~IIIB~ envelope (Env) gene for the induction of Env‐specific cellular immunity.

Results

The virus titers of the constructed rAd5 were similar to that of the parental Ad5 vector. Furthermore, high‐dose immunization of rAd5 induced Env‐specific CD8^+^ cells and high levels of anti‐ELDKWA antibodies. Moreover, an in vitro HIV‐1 neutralization assay indicated that ELDKWA‐specific mAbs derived from rAd5‐immunized mice neutralized a wide range of HIV‐1 strains.

Conclusions

The present study outlines the development of an Ad5‐based HIV‐1 vaccine targeting the hypervariable regions of Ad5. The constructed rAd5 induced an HIV‐1‐specific cellular immune response and neutralizing antibodies against various strains of HIV‐1 simultaneously. Copyright © 2008 John Wiley & Sons, Ltd.