title: Phase I/II randomized trial of safety and immunogenicity of LIPO-5 alone, ALVAC-HIV (vCP1452) alone, and ALVAC-HIV (vCP1452) prime/LIPO-5 boost in healthy, HIV-1-uninfected adult participants.
abstract: Finding an effective human immunodeficiency virus type 1 (HIV-1) vaccine remains a major global health priority. In a phase I/II, placebo-controlled trial, healthy, HIV-1-negative adults were randomized to receive one of 5 vaccine regimens: LIPO-5 (combination of 5 lipopeptides) alone (250 μg), ALVAC-HIV (vCP1452) alone, or 3 groups of ALVAC-HIV (vCP1452) followed by ALVAC-HIV (vCP1452) plus LIPO-5 (250, 750, and 2,500 μg). Only 73/174 participants (42%) received all four vaccinations due to a study halt related to myelitis. There were no significant differences in systemic reactions between groups or in local reactogenicity between groups receiving ALVAC-HIV (vCP1452). Significant differences in local reactogenicity occurred between groups receiving LIPO-5 (P ≤ 0.05). Gag and Env antibodies were undetectable by ELISA 2 weeks after the fourth vaccination for all but one recipient. Antibodies to Gag and Env were present in 32% and 24% of recipients of ALVAC-HIV (vCP1452) alone and in 47% and 35% of ALVAC-HIV (vCP1452)+LIPO recipients, respectively. Coadministration of LIPO-5 did not significantly increase the response rate compared to ALVAC-HIV (vCP1452) alone, nor was there a significant relationship between dose and antibody responses among ALVAC-HIV (vCP1452)+LIPO groups. Over 90% of study participants had no positive gamma interferon (IFN-γ) enzyme-linked immunosorbent spot assay (ELISpot) responses to any peptide pool at any time point. The study was halted due to a case of myelitis possibly related to the LIPO-5 vaccine; this case of myelitis remains an isolated event. In general, there was no appreciable cell-mediated immunity detected in response to the vaccines used in this study, and antibody responses were limited. The clinical trial is registered on ClinicalTrials.gov with registry number NCT00076063.
authors.affiliation: Department of Internal Medicine, Saint Louis University, St. Louis, Missouri, USA freyse@slu.edu.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Frey
authors.affiliation: Department of Medicine, University of California, San Francisco, California, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Peiperl
authors.affiliation: Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, Washington, USA.
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.affiliation: Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Spyros
authors.initials: S
authors.lastname: Kalams
authors.affiliation: Department of Medicine, University of Alabama, Birmingham, Alabama, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
authors.affiliation: Department of Medicine, University of Medicine, University of Rochester School of Medicine & Dentistry, Rochester, New York, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.affiliation: Department of Medicine, Alpert Medical School of Brown University, Providence, Rhode Island, USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lally
authors.affiliation: The Fenway Institute, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Mayer
authors.affiliation: Institute of Human Virology, University of Maryland, Baltimore, Maryland, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Blattner
authors.affiliation: Center for Immunization Research, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Clayton D
authors.initials: CD
authors.lastname: Harro
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, New York, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Hammer
authors.affiliation: Department of Internal Medicine, Saint Louis University, St. Louis, Missouri, USA.
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Gorse
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: John
authors.initials: J
authors.lastname: Hural
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Inserm, U955, Equipe 16, Université Paris Est, Faculté de Médecine, Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Levy
authors.affiliation: SCHARP Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Gilbert
authors.affiliation: SCHARP Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: deCamp
authors.affiliation: Bill & Melinda Gates Foundation, Seattle, Washington, USA.
authors.forename: Nina D
authors.initials: ND
authors.lastname: Russell
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Marnie
authors.initials: M
authors.lastname: Elizaga
authors.affiliation: AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Allen
authors.affiliation: Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, Washington, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D000293:Adolescent; D000328:Adult; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D016896:Treatment Outcome; D014611:Vaccination / Q000009:adverse effects* / Q000379:methods*; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D010919:Placebos; D007371:Interferon-gamma