title: Long-term CD4(+) and CD8(+) T-cell responses induced in HIV-uninfected volunteers following intradermal or intramuscular administration of an HIV-lipopeptide vaccine (ANRS VAC16).
abstract: BACKGROUND
  We have shown that the intradermal (ID) administration of an HIV-1 lipopeptide candidate vaccine (LIPO-4) is well tolerated in healthy volunteers, with one fifth the IM dose delivered by this route inducing HIV-1-specific CD8(+) T-cell responses of a magnitude and quality similar to those achieved by IM administration. In this long-term follow-up, we aimed to investigate the sustainability and epitopic breadth of the immune responses induced.
  
  
  METHODS
  In a prospective multicentre trial, 68 healthy volunteers were randomised to receive, at weeks 0, 4 and 12, either a 0.5 ml IM (500 μg of each lipopeptide; 35 volunteers) dose or a 0.1 ml ID (100 μg of each lipopeptide; 33 volunteers) dose of the LIPO-4 vaccine, in the deltoid region of the non-dominant arm. All 68 volunteers received the first two vaccinations, and 44 volunteers in the ID group and 22 in the IM group received the third. We describe here the long-term CD8(+) and CD4(+) T-cell immune responses, up to 48 weeks after the first immunisation.
  
  
  RESULTS
  Response frequency was highest at week 14 for CD4(+) T cells, at 85% (28/33) for the IM group and 61% (20/33) for the ID group (p=0.027), and at week 48 for CD8(+) T cells, at 36% (12/33) for the ID group and 31% (11/35) for the IM group (p=0.67). Response rates tended to be lower for volunteers receiving the third vaccination boost, whether IM or ID. Finally, we also observed a striking change in the specificity of the CD8(+) T-cell responses induced shortly (2 weeks) or several months (48 weeks) after LIPO-4 vaccination.
  
  
  CONCLUSIONS
  Lipopeptide vaccines elicited sustainable CD4(+) and CD8(+) T-cell responses, following IM or ID administration. CD8(+) T-cell responses had shifted and expanded to different epitopes after one year of follow-up. These results should facilitate the design of the next generation of prime-boost trials with repeated doses of lipopeptide vaccines.
authors.affiliation: Université Paris Descartes, Faculté de Médecine, Inserm, CIC BT505, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Cochin, CIC de Vaccinologie Cochin-Pasteur, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France. odile.launay@cch.aphp.fr
authors.forename: Odile
authors.initials: O
authors.lastname: Launay
authors.forename: Mathieu
authors.initials: M
authors.lastname: Surenaud
authors.forename: Corinne
authors.initials: C
authors.lastname: Desaint
authors.forename: Nadine
authors.initials: N
authors.lastname: Ben Hamouda
authors.forename: Gilles
authors.initials: G
authors.lastname: Pialoux
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Bonnet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Poizot-Martin
authors.forename: Gustavo
authors.initials: G
authors.lastname: Gonzales
authors.forename: Lise
authors.initials: L
authors.lastname: Cuzin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bourgault-Villada
authors.forename: Yves
authors.initials: Y
authors.lastname: Lévy
authors.forename: Jeannine
authors.initials: J
authors.lastname: Choppin
authors.forename: Christine
authors.initials: C
authors.lastname: Durier
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology; D064368:Healthy Volunteers; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D055666:Lipopeptides / Q000008:administration & dosage / Q000276:immunology*; D011446:Prospective Studies; D014611:Vaccination / Q000379:methods
chemical_list: D016915:AIDS Vaccines; D055666:Lipopeptides; D007371:Interferon-gamma
keywords: HIV-1 vaccine; Intradermal injection; Lipopeptides; Randomised trial