Cellular immune responses induced with dose-sparing intradermal administration of HIV vaccine to HIV-uninfected volunteers in the ANRS VAC16 trial.
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.
Launay
Odile
O
Université Paris Descartes, Faculté de Médecine, Paris, France. odile.launay@cch.aphp.fr
Durier
Christine
C
Desaint
Corinne
C
Silbermann
Benjamin
B
Jackson
Angela
A
Pialoux
Gilles
G
Bonnet
Bénédicte
B
Poizot-Martin
Isabelle
I
Gonzalez-Canali
Gustavo
G
Cuzin
Lise
L
Figuereido
Suzanne
S
Surenaud
Mathieu
M
Ben Hamouda
Nadine
N
Gahery
Hanne
H
Choppin
Jeannine
J
Salmon
Dominique
D
Guérin
Corinne
C
Bourgault Villada
Isabelle
I
Guillet
Jean-Gérard
JG
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
D016915:AIDS Vaccines; D010455:Peptides; D014764:Viral Proteins
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