title: DNA and modified vaccinia virus Ankara vaccines encoding multiple cytotoxic and helper T-lymphocyte epitopes of human immunodeficiency virus type 1 (HIV-1) are safe but weakly immunogenic in HIV-1-uninfected, vaccinia virus-naive adults.
abstract: We evaluated a DNA plasmid-vectored vaccine and a recombinant modified vaccinia virus Ankara vaccine (MVA-mBN32), each encoding cytotoxic and helper T-lymphocyte epitopes of human immunodeficiency virus type 1 (HIV-1) in a randomized, double-blinded, placebo-controlled trial in 36 HIV-1-uninfected adults using a heterologous prime-boost schedule. HIV-1-specific cellular immune responses, measured as interleukin-2 and/or gamma interferon production, were induced in 1 (4%) of 28 subjects after the first MVA-mBN32 immunization and in 3 (12%) of 25 subjects after the second MVA-mBN32 immunization. Among these responders, polyfunctional T-cell responses, including the production of tumor necrosis factor alpha and perforin, were detected. Vaccinia virus-specific antibodies were induced to the MVA vector in 27 (93%) of 29 and 26 (93%) of 28 subjects after the first and second immunizations with MVA-mBN32. These peptide-based vaccines were safe but were ineffective at inducing HIV-1-specific immune responses and induced much weaker responses than MVA vaccines expressing the entire open reading frames of HIV-1 proteins.
authors.affiliation: Division of Infectious Diseases, Allergy, and Immunology, Department of Internal Medicine, School of Medicine, Saint Louis University, St. Louis, Missouri, USA. gorsegj@slu.edu
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Gorse
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Newman
authors.forename: Allan
authors.initials: A
authors.lastname: deCamp
authors.forename: Christine Mhorag
authors.initials: CM
authors.lastname: Hay
authors.forename: Stephen C
authors.initials: SC
authors.lastname: De Rosa
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Noonan
authors.forename: Brian D
authors.initials: BD
authors.lastname: Livingston
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Fuchs
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Kalams
authors.forename: Farah L
authors.initials: FL
authors.lastname: Cassis-Ghavami
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D054353:Perforin / Q000096:biosynthesis; D010919:Placebos / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D014765:Viral Vaccines; D054353:Perforin; D007371:Interferon-gamma