title: Single-cycle immunodeficiency viruses provide strategies for uncoupling in vivo expression levels from viral replicative capacity and for mimicking live-attenuated SIV vaccines.
abstract: To reduce the risks associated with live-attenuated immunodeficiency virus vaccines, single-cycle immunodeficiency viruses (SCIVs) were developed by primer complementation and production of the vaccine in the absence of vif in a vif-independent cell line. After a single intravenous injection of SCIVs into rhesus monkeys, peak viral RNA levels of 10(3) to 10(4) copies/ml plasma were observed, indicating efficient expression of SCIV in the vaccinee. After booster immunizations with SCIVs, SIV-specific humoral and cellular immune responses were observed. Although the vaccine doses used in this pilot study could not protect vaccinees from subsequent intravenous challenge with pathogenic SIVmac239, our results demonstrate that the novel SCIV approach allows us to uncouple in vivo expression levels from the viral replicative capacity facilitating the analysis of the relationship between viral expression levels or viral genes and immune responses induced by SIV.
authors.affiliation: Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Seraphin
authors.initials: S
authors.lastname: Kuate
authors.forename: Christiane
authors.initials: C
authors.lastname: Stahl-Hennig
authors.forename: Peter
authors.initials: P
authors.lastname: ten Haaft
authors.forename: Jonathan
authors.initials: J
authors.lastname: Heeney
authors.forename: Klaus
authors.initials: K
authors.lastname: Uberla
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001483:Base Sequence; D002478:Cells, Cultured; D016341:Genes, vif; D005822:Genetic Vectors; D007117:Immunization, Secondary; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009154:Mutation; D016366:Open Reading Frames; D010865:Pilot Projects; D012343:RNA, Transfer / Q000235:genetics; D012367:RNA, Viral / Q000097:blood; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D013997:Time Factors; D019562:Viral Load; D015678:Viral Structural Proteins / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D012367:RNA, Viral; D018449:SAIDS Vaccines; D015678:Viral Structural Proteins; D012343:RNA, Transfer