title: Live attenuated rubella viral vectors stably express HIV and SIV vaccine antigens while reaching high titers.
abstract: Live attenuated viruses make potent and effective vaccines. Despite the urgent need for an HIV vaccine, this approach has not been feasible, since it has not been possible to attenuate the virus reliably and guarantee vaccine safety. Instead, live viral vectors have been proposed that could present HIV vaccine antigens in the most immunogenic way, in the context of an active infection. We have adapted the rubella vaccine strain RA27/3 as a vector to express HIV and SIV antigens, and tested the effect of insert size and composition on vector stability and viral titer. We have identified an acceptor site in the rubella nonstructural gene region, where foreign genes can be expressed as a fusion protein with the nonstructural protein P150 without affecting essential viral functions. The inserts were expressed as early genes of rubella, under control of the rubella genomic promoter. At this site, HIV and SIV antigens were expressed stably for at least seven passages, as the rubella vectors reached high titers. Rubella readily infects rhesus macaques, and these animals will provide an ideal model for testing the new vectors for replication in vivo, immunogenicity, and protection against SIV or SHIV challenge.
authors: Lab of Immunoregulation, Division of Viral Products, Office of Vaccines, Center for Biologics, FDA, NIH Campus, Bethesda, MD 20892, USA.
authors: Konstantin
authors: K
authors: Virnik
authors: Yisheng
authors: Y
authors: Ni
authors: Ira
authors: I
authors: Berkower
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics* / Q000276:immunology; D002522:Chlorocebus aethiops; D000939:Epitopes / Q000235:genetics; D015683:Gene Products, gag / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012412:Rubella virus / Q000235:genetics* / Q000276:immunology; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D014613:Vaccines, Attenuated / Q000235:genetics* / Q000276:immunology*; D014709:Vero Cells / Q000821:virology; D019562:Viral Load / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics
chemical_list: D016915:AIDS Vaccines; D000956:Antigens, Viral; D000939:Epitopes; D015683:Gene Products, gag; D015488:HIV Antigens; D011994:Recombinant Proteins; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated; D017361:Viral Nonstructural Proteins