title: Designed recombinant adenovirus type 5 vector induced envelope-specific CD8(+) cytotoxic T lymphocytes and cross-reactive neutralizing antibodies against human immunodeficiency virus type 1.
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.
authors.affiliation: Department of Molecular Biodefence Research, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Ura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yoshida
authors.forename: Ke-Qin
authors.initials: KQ
authors.lastname: Xin
authors.forename: Shinji
authors.initials: S
authors.lastname: Yoshizaki
authors.forename: Sayaka
authors.initials: S
authors.lastname: Yashima
authors.forename: Shinya
authors.initials: S
authors.lastname: Abe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Okuda
mesh_terms: 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*
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D004274:DNA, Recombinant; D015700:HIV Envelope Protein gp41; C514787:gp41 protein, Human immunodeficiency virus 1