title: Safety and immunogenicity of a CTL multiepitope peptide vaccine for HIV with or without GM-CSF in a phase I trial.
abstract: There is an urgent need for a vaccine capable of preventing HIV infection or the development of HIV-related disease. A number of approaches designed to stimulate HIV-specific CD8+ cytotoxic T cell responses together with helper responses are presently under evaluation. In this phase 1, multi-center, placebo-controlled trial, we tested the ability of a novel multiepitope peptide vaccine to elicit HIV-specific immunity. To enhance the immunogenicity of the peptide vaccine, half of the vaccine recipients received recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) protein as a coadjuvant. The vaccine was safe; tolerability was moderate, with a number of adverse events related to local injection site reactogenicity. Anti-GM-CSF antibody responses developed in the majority of GM-CSF recipients but were not associated with adverse hematologic events. The vaccine was only minimally immunogenic. Six of 80 volunteers who received vaccine developed HIV-specific responses as measured by interferon-gamma ELISPOT assay, and measurable responses were transient. This study failed to demonstrate that GM-CSF can substantially improve the overall weak immunogenicity of a multiepitope peptide-based HIV vaccine.
authors.affiliation: Department of Pediatrics, Pediatric Infectious Diseases, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA 30322, United States. paul.spearman@emory.edu
authors.forename: Paul
authors.initials: P
authors.lastname: Spearman
authors.forename: Spyros
authors.initials: S
authors.lastname: Kalams
authors.forename: Marnie
authors.initials: M
authors.lastname: Elizaga
authors.forename: Barbara
authors.initials: B
authors.lastname: Metch
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Chiu
authors.forename: Mary
authors.initials: M
authors.lastname: Allen
authors.forename: Kent J
authors.initials: KJ
authors.lastname: Weinhold
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: Scott D
authors.initials: SD
authors.lastname: Parker
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Frey
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Fuchs
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.forename: Michael D
authors.initials: MD
authors.lastname: Lubeck
authors.forename: Michael
authors.initials: M
authors.lastname: Egan
authors.forename: Ralph
authors.initials: R
authors.lastname: Braun
authors.forename: John H
authors.initials: JH
authors.lastname: Eldridge
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011994:Recombinant Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D010446:Peptide Fragments; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor