title: Phase I trial of a CD8+ T-cell peptide epitope-based vaccine for infectious mononucleosis.
abstract: A single blind, randomized, placebo-controlled, single-center phase I clinical trial of a CD8(+) T-cell peptide epitope vaccine against infectious mononucleosis was conducted with 14 HLA B*0801-positive, Epstein-Barr virus (EBV)-seronegative adults. The vaccine comprised the HLA B*0801-restricted peptide epitope FLRGRAYGL and tetanus toxoid formulated in a water-in-oil adjuvant, Montanide ISA 720. FLRGRAYGL-specific responses were detected in 8/9 peptide-vaccine recipients and 0/4 placebo vaccine recipients by gamma interferon enzyme-linked immunospot assay and/or limiting-dilution analysis. The same T-cell receptor Vbeta CDR3 sequence that is found in FLRGRAYGL-specific T cells from most EBV-seropositive individuals could also be detected in the peripheral blood of vaccine recipients. The vaccine was well tolerated, with the main side effect being mild to moderate injection site reactions. After a 2- to 12-year follow-up, 1/2 placebo vaccinees who acquired EBV developed infectious mononucleosis, whereas 4/4 vaccinees who acquired EBV after completing peptide vaccination seroconverted asymptomatically. Single-epitope vaccination did not predispose individuals to disease, nor did it significantly influence development of a normal repertoire of EBV-specific CD8(+) T-cell responses following seroconversion.
authors.affiliation: Queensland Institute of Medical Research, P.O. Royal Brisbane Hospital, Queensland 4029, Australia.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Elliott
authors.forename: Andreas
authors.initials: A
authors.lastname: Suhrbier
authors.forename: John J
authors.initials: JJ
authors.lastname: Miles
authors.forename: Greg
authors.initials: G
authors.lastname: Lawrence
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Pye
authors.forename: Thuy T
authors.initials: TT
authors.lastname: Le
authors.forename: Andrew
authors.initials: A
authors.lastname: Rosenstengel
authors.forename: Tam
authors.initials: T
authors.lastname: Nguyen
authors.forename: Anthony
authors.initials: A
authors.lastname: Allworth
authors.forename: Scott R
authors.initials: SR
authors.lastname: Burrows
authors.forename: John
authors.initials: J
authors.lastname: Cox
authors.forename: David
authors.initials: D
authors.lastname: Pye
authors.forename: Denis J
authors.initials: DJ
authors.lastname: Moss
authors.forename: Mandvi
authors.initials: M
authors.lastname: Bharadwaj
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000276:immunology*; D022283:Herpesvirus Vaccines / Q000276:immunology*; D006801:Humans; D007244:Infectious Mononucleosis / Q000276:immunology / Q000517:prevention & control*; D008353:Mannitol / Q000008:administration & dosage / Q000031:analogs & derivatives; D009829:Oleic Acids / Q000008:administration & dosage; D016037:Single-Blind Method; D013745:Tetanus Toxoid / Q000008:administration & dosage; D022223:Vaccines, Subunit / Q000009:adverse effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; D022283:Herpesvirus Vaccines; D009829:Oleic Acids; D013745:Tetanus Toxoid; D022223:Vaccines, Subunit; C001681:mannide monooleate; D008353:Mannitol