title: Live attenuated rubella vectors expressing SIV and HIV vaccine antigens replicate and elicit durable immune responses in rhesus macaques.
abstract: BACKGROUND
  Live attenuated viruses are among our most potent and effective vaccines. For human immunodeficiency virus, however, a live attenuated strain could present substantial safety concerns. We have used the live attenuated rubella vaccine strain RA27/3 as a vector to express SIV and HIV vaccine antigens because its safety and immunogenicity have been demonstrated in millions of children. One dose protects for life against rubella infection. In previous studies, rubella vectors replicated to high titers in cell culture while stably expressing SIV and HIV antigens. Their viability in vivo, however, as well as immunogenicity and antibody persistence, were unknown.
  
  
  RESULTS
  This paper reports the first successful trial of rubella vectors in rhesus macaques, in combination with DNA vaccines in a prime and boost strategy. The vectors grew robustly in vivo, and the protein inserts were highly immunogenic. Antibody titers elicited by the SIV Gag vector were greater than or equal to those elicited by natural SIV infection. The antibodies were long lasting, and they were boosted by a second dose of replication-competent rubella vectors given six months later, indicating the induction of memory B cells.
  
  
  CONCLUSIONS
  Rubella vectors can serve as a vaccine platform for safe delivery and expression of SIV and HIV antigens. By presenting these antigens in the context of an acute infection, at a high level and for a prolonged duration, these vectors can stimulate a strong and persistent immune response, including maturation of memory B cells. Rhesus macaques will provide an ideal animal model for demonstrating immunogenicity of novel vectors and protection against SIV or SHIV challenge.
authors.affiliation: Lab of Immunoregulation, Division of Viral Products, Office of Vaccines, Center for Biologics, FDA, NIH Campus, Bethesda, MD 20892, USA. ira.berkower@fda.hhs.gov.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Virnik
authors.forename: Max
authors.initials: M
authors.lastname: Hockenbury
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Ni
authors.forename: Joel
authors.initials: J
authors.lastname: Beren
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
authors.forename: Ira
authors.initials: I
authors.lastname: Berkower
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D004337:Drug Carriers; D006678:HIV / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory; D008253:Macaca mulatta; D012412:Rubella virus / Q000235:genetics / Q000254:growth & development*; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D013997:Time Factors; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D000956:Antigens, Viral; D004337:Drug Carriers; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated
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