Recombinant vaccinia DIs expressing simian immunodeficiency virus gag and pol in mammalian cells induces efficient cellular immunity as a safe immunodeficiency virus vaccine candidate

• Published in: Microbiology and immunology Vol. 50; no. 12; p. 989
• Main Authors: Okamura, Tomotaka, Someya, Kenji, Matsuo, Kazuhiro, Hasegawa, Atsuhiko, Yamamoto, Naoki, Honda, Mitsuo
• Format: Journal Article
• Language: English
• Published: Australia 2006
• Subjects: Animals; Genes, gag - immunology; Genes, pol - immunology; Immunity, Cellular - drug effects; Mice; Mice, Inbred BALB C; Recombination, Genetic; SAIDS Vaccines - administration & dosage; SAIDS Vaccines - genetics; SAIDS Vaccines - immunology; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus - chemistry; Simian Immunodeficiency Virus - genetics; Simian Immunodeficiency Virus - immunology; Vaccinia virus - genetics
• ISSN: 0385-5600; 1348-0421
• DOI: 10.1111/j.1348-0421.2006.tb03867.x

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.