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Hemagglutinating virus of Japan protein is efficient for induction of CD4+ T-cell response by a hepatitis B core particle-based HIV vaccine
Authors:Takeda Satoshi  Shiosaki Kouichi  Kaneda Yasufumi  Nakasatomi Tetsuya  Yoshizaki Hitomi  Someya Kenji  Konno Yusuke  Eda Yasuyuki  Kino Youichirou  Yamamoto Naoki  Honda Mitsuo
Affiliation:AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Abstract:By using the hepatitis B core (HBc) protein gene as a carrier, HIV-1 env V3 gene was inserted into the carrier gene, and the HIV gene was expressed inside a chimeric HIV-HBc particle (HIV-HBc), which was a unique candidate for induction of HIV-specific CTL activity. This was seen significantly in mice without the need of an adjuvant, because other responses specific for the HIV peptide such as T-cell proliferation and antibody production were not induced. However, when hemagglutinating virus of Japan (HVJ) protein was incorporated into an anionic liposome containing HIV peptide (HIV-HVJ-liposome) and was used as a booster immunization in HIV-HBc primed animals, the HIV-specific T-cell response and enhanced CTL activity were clearly induced in consecutively immunized animals. Furthermore, the HIV-specific humoral immune response was also induced and a neutralization activity was detected in the immune sera. Thus, when an HIV peptide antigen is expressed inside the virus like a particle of HBc, it can induce both cellular and humoral immunities when an HVJ-HIV-liposome, but not an HIV-liposome, is inoculated as the booster antigen. The HVJ-stimulated splenocytes secreted IL-18 and IL-12 to synergistically enhance the secretion of IFN-gamma in vitro. These findings suggest that the HVJ protein is effective at inducing the HIV-specific immunities, if used as part of a booster antigen in the consecutive immunization regimen.
Keywords:HVJ protein-incorporated liposome  HIV-hepatitis B core chimeric protein  HIV-specific immunity  Synergy of IL-18 and -12 to secrete IFN-γ  HVJ  hemagglutinating virus of Japan  HBc  hepatitis B core protein  HIV-HBc  chimeric HIV-V3-HBc particle  HVJ-liposome  liposome with incorporated HVJ protein  HIV-liposome  liposome which encapsulated circular HIV-V3 peptide  HIV-HVJ-liposome  HVJ-liposome which encapsulated HIV-V3 circular peptide  V3  principal neutralizing determinant  KLH  keyhole limpet hemocyanin  KLH-IIIB  BSA-IIIB  Chol  Cholesterol  PC  phosphatidylcholine  Sph  shingomyelin  DOPE  dioleoylphosphatidylethanolamine  DC-chol  dimethylaminoethane carbamoyl-cholesterol  HAU  hemagglutinating unit  SI  stimulation index
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