The degree of apoptosis as an immunostimulant for a DNA vaccine against HIV-1 infection.
To regulate the expression of the apoptotic gene, we constructed bicistronic DNA vaccines that encode for HIV env and caspase-3 mutant (casp 3m) that are expressed via the encephalomyocarditis virus internal ribosomal entry site (IRES) or cytomegalovirus (CMV) promoter-dependent translations. While IRES-casp 3m induced weak apoptosis and caused little reduction in antigen expression, CMV-casp 3m elicited strong apoptosis and led to a marked decrease in the antigen expression. Therefore, IRES-casp 3m augmented HIV-specific immune responses, and IRES-casp 3m induced significant protection against the vaccinia-HIV chimeric virus. These results suggest that the appropriate level of apoptosis is important for DNA vaccine development.
Kojima
Yoshitsugu
Y
Department of Molecular Biodefense Research, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Jounai
Nao
N
Takeshita
Fumihiko
F
Nakazawa
Masatoshi
M
Okuda
Kentaro
K
Watabe
Setsuko
S
Xin
Ke-Qin
KQ
Okuda
Kenji
K
D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D015153:Blotting, Western; D020169:Caspases / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004279:DNA, Viral / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D049449:Luminescence; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019444:Vaccines, DNA / Q000276:immunology; D014615:Vaccinia / Q000517:prevention & control; D014616:Vaccinia virus / Q000472:pathogenicity; D014759:Viral Envelope Proteins / Q000276:immunology
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D016207:Cytokines; D004279:DNA, Viral; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D008156:Luciferases; D020169:Caspases