Session 51Poster Presentations Novel Vaccine Approaches Session Day and Time: Thursday 1:30 - 3:30 pm Room: Hall D
425 Comparison between Intradermal and Intramuscular Routes of Administration in the Induction of Multispecific CD8+ Lymphocytes in Rhesus Macaques Vaccinated with NEF and GAG Derived Lipopeptides Z. Coutsinos*1, P. Villefroy1, H. Gras-Masse2, C. Beyer3, J. G. Guillet1, I. Bourgault-Villada1 1Cochin Inst, Paris, France; 2Lab Synthesis, Structure and Function of Biomolecules, Inst Pasteur de Lille; and 3Inst of Virology, Faculty of Med, Univ Pasteur de Strasbourg
Background: The importance of cytotoxic T-lymphocytes (CTLs) in the control of HIV/SIV replication is well documented. Magnitude and breadth of CTL responses are factors that are likely to influence the effectiveness of CTLs. Indeed broad multi-specific CTLs, induced by vaccination, control viral load, and appear to retard disease progression in infected macaques. Thus, in the aim to develop and efficient HIV vaccine, the optimization of approaches which induce multi-epitopic CTL responses in vivo using synthetic constructions is of great interest. In particular, lipopeptide vaccination has revealed promising results. Indeed lipopeptides have been shown to be highly immunogenic in vivo, inducing strong cell mediated immune responses. Given that the route of immunization plays an important role in the development of an effective immune response, the present study was designed to assess lipopeptide immunizations administered by 2 different routes in their ability to elicit virus specific T-lymphocytes in the rhesus macaque.
Methods: Two (2) cohorts of 4 macaques were vaccinated either by the intramuscular or the intradermal route with a mixture of 7 lipopeptides, 5 of which were derived from SIV-NEF and 2 from SIV-GAG. The animals received 3 immunizations at 3 wk intervals. We investigated the T-cell effector responses directed against a large number of SIV-epitopic peptides, included in the immunizing sequences, by performing a sensitive IFNg ELISpot assay.
Results: Antigen-specific responses were observed between 7 and 11 wks post-vaccination in both groups. Macaques immunized by the intramuscular route yielded antigen specific IFNg secreting lymphocytes in response to no more than 2 pools of short peptides derived from SIV-NEF. In contrast, intradermally immunized macaques presented multi-specific IFNg-secreting lymphocytes in response to as many as 4 pools of short peptides derived from SIV-NEF and/or -GAG. Responses persisted 16 wks following the vaccination protocol in one of the ID vaccinated macaques.
Conclusions: Our results suggest that the route by which SIV-lipopeptides are administered affects the breadth and the durability of the cellular immune response. Lipopeptides injected intradermally elicit broader multi-specific T-cell responses as compared to intramuscular administrations.
