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

Abstract

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.

• Authors: Tomotaka Okamura, Kenji Someya, Kazuhiro Matsuo, Atsuhiko Hasegawa, Naoki Yamamoto, Mitsuo Honda
• Journal: Microbiology and immunology (Microbiol Immunol) Vol. 50 Issue 12 Pg. 989-1000 ( 2006) ISSN: 0385-5600 [Print] Australia
• PMID: 17179668 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• SAIDS Vaccines

Topics

• Animals
• Genes, gag (immunology)
• Genes, pol (immunology)
• Immunity, Cellular (drug effects)
• Mice
• Mice, Inbred BALB C
• Recombination, Genetic
• SAIDS Vaccines (administration & dosage, genetics, immunology)
• Simian Acquired Immunodeficiency Syndrome
• Simian Immunodeficiency Virus (chemistry, genetics, immunology)
• Vaccinia virus (genetics)