title: Immunogenicity of a recombinant measles-HIV-1 clade B candidate vaccine.
abstract: Live attenuated measles virus is one of the most efficient and safest vaccines available, making it an attractive candidate vector for a HIV/AIDS vaccine aimed at eliciting cell-mediated immune responses (CMI). Here we have characterized the potency of CMI responses generated in mice and non-human primates after intramuscular immunisation with a candidate recombinant measles vaccine carrying an HIV-1 insert encoding Clade B Gag, RT and Nef (MV1-F4). Eight Mauritian derived, MHC-typed cynomolgus macaques were immunised with 10(5) TCID(50) of MV1-F4, four of which were boosted 28 days later with the same vaccine. F4 and measles virus (MV)-specific cytokine producing T cell responses were detected in 6 and 7 out of 8 vaccinees, respectively. Vaccinees with either M6 or recombinant MHC haplotypes demonstrated the strongest cytokine responses to F4 peptides. Polyfunctional analysis revealed a pattern of TNFα and IL-2 responses by CD4+ T cells and TNFα and IFNγ responses by CD8+ T cells to F4 peptides. HIV-specific CD4+ and CD8+ T cells expressing cytokines waned in peripheral blood lymphocytes by day 84, but CD8+ T cell responses to F4 peptides could still be detected in lymphoid tissues more than 3 months after vaccination. Anti-F4 and anti-MV antibody responses were detected in 6 and 8 out of 8 vaccinees, respectively. Titres of anti-F4 and MV antibodies were boosted in vaccinees that received a second immunisation. MV1-F4 carrying HIV-1 Clade B inserts induces robust boostable immunity in non-human primates. These results support further exploration of the MV1-F4 vector modality in vaccination strategies that may limit HIV-1 infectivity.
authors.affiliation: Division of Biotherapeutics, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, United Kingdom. rstebbings@nibsc.ac.uk
authors.forename: Richard
authors.initials: R
authors.lastname: Stebbings
authors.forename: Michèle
authors.initials: M
authors.lastname: Février
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Clarisse
authors.initials: C
authors.lastname: Lorin
authors.forename: Marguerite
authors.initials: M
authors.lastname: Koutsoukos
authors.forename: Edward
authors.initials: E
authors.lastname: Mee
authors.forename: Nicola
authors.initials: N
authors.lastname: Rose
authors.forename: Joanna
authors.initials: J
authors.lastname: Hall
authors.forename: Mark
authors.initials: M
authors.lastname: Page
authors.forename: Neil
authors.initials: N
authors.lastname: Almond
authors.forename: Gerald
authors.initials: G
authors.lastname: Voss
authors.forename: Frédéric
authors.initials: F
authors.lastname: Tangy
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D008252:Macaca fascicularis; D008297:Male; D008458:Measles Vaccine / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D051379:Mice; D012194:RNA-Directed DNA Polymerase / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D014614:Vaccines, Synthetic; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015683:Gene Products, gag; D007376:Interleukin-2; D008458:Measles Vaccine; D014409:Tumor Necrosis Factor-alpha; D014614:Vaccines, Synthetic; D054311:nef Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma; D012194:RNA-Directed DNA Polymerase