Recombinant vaccinia DIs expressing simian immunodeficiency virus gag and pol in mammalian cells induces efficient cellular immunity as a safe immunodeficiency virus vaccine candidate.
A highly attenuated vaccinia virus substrain of Dairen-I (DIs) shows promise as a candidate vector for eliciting positive immunity against immune deficiency virus. DIs was randomly obtained by serial 1-day egg passages of a chorioarantoic membrane-adapted Dairen strain (DIE), resulting in substantial genomic deletion, including various genes regulating the virus-host-range. To investigate the impact of that deletion and of the subsequent insertion of a foreign gene into that region of DIs on the ability of the DIs recombinant to induce antigen-specific immunity, we generated a recombinant vaccinia DIs expressing fulllength gag and pol genes of simian immunodeficiency virus (SIV) (rDIsSIV gag/pol) and studied the biological and immunological characteristics of the recombinant natural mutant. The rDIsSIV gag/pol developed a tiny plaque on the chick embryo fibroblast (CEF). Viral particles of rDIsSIV gag/pol as well as SIV Gag-like particles were electromicroscopically detected in the cytoplasm. Interestingly, the recombinant DIs strain grows well in CEF cells but not in mammalian cells. While rDIsSIV gag/pol produces SIV proteins in mammalian HeLa and CV-1 cells, recombinant modified vaccinia Ankara strain (MVA) expressing SIV gag and pol genes (MVA/SIV239 gag/pol) clearly replicates in HeLa and CV-1 cell lines under synchronized growth conditions and produces the SIV protein in all cell lines. Moreover, intradermal administration of rDIsSIV gag/pol or of MVA/SIV239 gag/pol elicited similar levels of IFN-gamma spot-forming cells specific for SIV Gag. If the non-productive infection characteristically induced by recombinant DIs is sufficient to trigger immune induction, as we believe it is, then a human immunodeficiency virus vaccine employing the DIs recombinant would have the twin advantages of being both effective and safe.
Okamura
Tomotaka
T
AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.
Someya
Kenji
K
Matsuo
Kazuhiro
K
Hasegawa
Atsuhiko
A
Yamamoto
Naoki
N
Honda
Mitsuo
M
D000818:Animals; D015750:Genes, gag / Q000276:immunology*; D015751:Genes, pol / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D011995:Recombination, Genetic; D018449:SAIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome; D015302:Simian Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics
D018449:SAIDS Vaccines