Designed recombinant adenovirus type 5 vector induced envelope-specific CD8(+) cytotoxic T lymphocytes and cross-reactive neutralizing antibodies against human immunodeficiency virus type 1.
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.
Ura
Takehiro
T
Department of Molecular Biodefence Research, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Yoshida
Atsushi
A
Xin
Ke-Qin
KQ
Yoshizaki
Shinji
S
Yashima
Sayaka
S
Abe
Shinya
S
Mizuguchi
Hiroyuki
H
Okuda
Kenji
K
D016915:AIDS Vaccines / Q000276:immunology; D000260:Adenoviruses, Human / Q000145:classification / Q000235:genetics*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D004274:DNA, Recombinant / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D004274:DNA, Recombinant; D015700:HIV Envelope Protein gp41; C514787:gp41 protein, Human immunodeficiency virus 1