title: Induction of human immunodeficiency virus type 1-specific T cells by a bluetongue virus tubule-vectored vaccine prime-recombinant modified virus Ankara boost regimen.
abstract: In the absence of strategies for reliable induction of antibodies broadly neutralizing human immunodeficiency virus type 1 (HIV-1), vaccine efforts have shifted toward the induction of cell-mediated immunity. Here we describe the construction and immunogenicity of novel T-cell vaccine NS1.HIVA, which delivers the HIV-1 clade A consensus-derived immunogen HIVA on the surface of tubular structures spontaneously formed by protein NS1 of bluetongue virus. We demonstrated that NS1 tubules can accommodate a protein as large as 527 amino acids without losing their self-assembly capability. When injected into BALB/c mice by several routes, chimeric NS1.HIVA tubules induced HIV-1-specific major histocompatibility complex class I-restricted T cells. These could be boosted by modified virus Ankara expressing the same immunogen and generate a memory capable of gamma interferon (IFN-gamma) production, proliferation, and lysis of sensitized target cells. Induced memory T cells readily produced IFN-gamma 230 days postimmunization, and upon a surrogate virus challenge, NS1.HIVA vaccine alone decreased the vaccinia virus vv.HIVA load in ovaries by 2 orders of magnitude 280 days after immunization. Thus, because of its T-cell immunogenicity and antigenic simplicity, the NS1 delivery system could serve as a priming agent for heterologous prime-boost vaccination regimens. Its usefulness in primates, including humans, remains to be determined.
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, United Kingdom.
authors.forename: Natasha
authors.initials: N
authors.lastname: Larke
authors.forename: Aileen
authors.initials: A
authors.lastname: Murphy
authors.forename: Christoph
authors.initials: C
authors.lastname: Wirblich
authors.forename: Denise
authors.initials: D
authors.lastname: Teoh
authors.forename: Marie J
authors.initials: MJ
authors.lastname: Estcourt
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Polly
authors.initials: P
authors.lastname: Roy
authors.forename: Tomás
authors.initials: T
authors.lastname: Hanke
mesh_terms: D000818:Animals; D001820:Bluetongue virus / Q000235:genetics / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis; D006801:Humans; D007117:Immunization, Secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D015483:HIV Antibodies; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014765:Viral Vaccines