title: Cellular immune responses induced with dose-sparing intradermal administration of HIV vaccine to HIV-uninfected volunteers in the ANRS VAC16 trial.
abstract: OBJECTIVE
  The objective was to compare the safety and cellular immunogenicity of intradermal versus intramuscular immunization with an HIV-lipopeptide candidate vaccine (LIPO-4) in healthy volunteers.
  
  
  METHODS
  A randomized, open-label trial with 24 weeks of follow-up was conducted in France at six HIV-vaccine trial sites. Sixty-eight healthy 21- to 55-year-old HIV-uninfected subjects were randomized to receive the LIPO-4 vaccine (four HIV lipopeptides linked to a T-helper-stimulating epitope of tetanus-toxin protein) at weeks 0, 4 and 12, either intradermally (0.1 ml, 100 microg of each peptide) or intramuscularly (0.5 ml, 500 microg of each peptide). Comparative safety of both routes was evaluated. CD8+ T-cell immune responses to HIV epitopes (ELISpot interferon-gamma assay) and tetanus toxin-specific CD4+ T-cell responses (lymphoproliferation) were assessed at baseline, two weeks after each injection, and at week 24.
  
  
  CONCLUSIONS
  No severe, serious or life-threatening adverse events were observed. Local pain was significantly more frequent after intramuscular injection, but local inflammatory reactions were more frequent after intradermal immunization. At weeks 2, 6, 14 and 24, the respective cumulative percentages of induced CD8+ T-cell responses to at least one HIV peptide were 9, 33, 39 and 52 (intradermal group) or 14, 20, 26 and 37 (intramuscular group), and induced tetanus toxin-specific CD4+ T-cell responses were 6, 27, 33 and 39 (intradermal), or 9, 46, 54 and 63 (intramuscular). In conclusion, intradermal LIPO-4 immunization was well tolerated, required one-fifth of the intramuscular dose, and induced similar HIV-specific CD8+ T-cell responses. Moreover, the immunization route influenced which antigen-specific T-cells (CD4+ or CD8+) were induced.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00121121.
authors: Université Paris Descartes, Faculté de Médecine, Paris, France. odile.launay@cch.aphp.fr
authors: Odile
authors: O
authors: Launay
authors: Christine
authors: C
authors: Durier
authors: Corinne
authors: C
authors: Desaint
authors: Benjamin
authors: B
authors: Silbermann
authors: Angela
authors: A
authors: Jackson
authors: Gilles
authors: G
authors: Pialoux
authors: Bénédicte
authors: B
authors: Bonnet
authors: Isabelle
authors: I
authors: Poizot-Martin
authors: Gustavo
authors: G
authors: Gonzalez-Canali
authors: Lise
authors: L
authors: Cuzin
authors: Suzanne
authors: S
authors: Figuereido
authors: Mathieu
authors: M
authors: Surenaud
authors: Nadine
authors: N
authors: Ben Hamouda
authors: Hanne
authors: H
authors: Gahery
authors: Jeannine
authors: J
authors: Choppin
authors: Dominique
authors: D
authors: Salmon
authors: Corinne
authors: C
authors: Guérin
authors: Isabelle
authors: I
authors: Bourgault Villada
authors: Jean-Gérard
authors: JG
authors: Guillet
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D000328:Adult; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D010455:Peptides; D014764:Viral Proteins
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