Evaluation of SIV-lipopeptide immunizations administered by the intradermal route in their ability to induce antigen specific T-cell responses in rhesus macaques.
Numerous clinical and experimental observations have shown that cellular immunity, in particular CD8+ T-lymphocytes, plays an important role in the control of HIV infection. We have focused on a lipopeptide vaccination strategy that has been shown to induce polyepitopic T-cell responses in both animals and humans, in order to deliver simian immunodeficiency virus (SIV) antigens to rhesus macaques. Given the relevance of antigen administration route in the development of an effective cellular immune response, this study was designed to assess SIV lipopeptide immunizations administered either by the intradermal (ID) or the intramuscular (IM) routes in their ability to elicit GAG and NEF multispecific T-lymphocytes in the rhesus macaque. Antigen specific T-cell responses were observed between 7 and 11 weeks following vaccination in both groups. Macaques immunized by the IM route yielded antigen-specific IFN-gamma secreting lymphocytes in response to no more than two pools of peptides derived from SIV-NEF. In contrast, among the four ID-immunized macaques, two presented multi-specific T-cell responses to as many as four pools of SIV-NEF and/or GAG peptides. Responses persisted 16 weeks following the vaccination protocol in one of the ID-vaccinated macaques. The induction of such responses is of great clinical relevance in the development of an effective HIV vaccine. Given the crucial role of CD8+ T-lymphocytes in HIV/SIV containment, vaccination through the intradermal route should merit high consideration in the development of an AIDS vaccine.
Coutsinos
Zoe
Z
Institut Cochin, Départment d'Immunologie, INSERM U567, CNRS UMR 8104, IFR Alfred Jost, Université René Descartes, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France.
Villefroy
Pascale
P
Gras-Masse
Helene
H
Guillet
Jean-Gerard
JG
Bourgault-Villada
Isabelle
I
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000235:genetics; D066298:In Vitro Techniques; D007271:Injections, Intradermal; D008074:Lipoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D018449:SAIDS Vaccines / Q000008:administration & dosage*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014764:Viral Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000956:Antigens, Viral; D000939:Epitopes; D008074:Lipoproteins; D010446:Peptide Fragments; D018449:SAIDS Vaccines; D014764:Viral Proteins