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Design Of Nanoparticular Carriers Targeting Toll Like Receptors For Vaccine Purpose

Design Of Nanoparticular Carriers Targeting Toll Like Receptors For Vaccine Purpose. XVIII International AIDS Conference 18 – 23 July 2010 Vienna, Austria. Vincent Pavot UMR 5086 CNRS/UCBL LYON (France) Bernard Verrier group. In vivo administration.

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Design Of Nanoparticular Carriers Targeting Toll Like Receptors For Vaccine Purpose

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  1. Design Of Nanoparticular Carriers TargetingTollLikeReceptors For Vaccine Purpose XVIII International AIDS Conference 18 – 23 July 2010 Vienna, Austria Vincent Pavot UMR 5086 CNRS/UCBL LYON (France) Bernard Verrier group

  2. In vivo administration • Particulate delivery-systems based on biodegradable polymers induction of broad humoral and cellular immune responses. • TLR are involved in innate immune response co delivering of an antigen and a TLR agonist amplify immune response against this antigen. We hypothesize that the adjunction of a co-stimulatory molecule TLR-3 agonist (poly(I:C)) will be a way of co-adjuvantation of p24 when co delivered by particles of either PLA (PolyLactic Acid) or Chitosan. p24 adorption on nacked NPs TLR agonist co-adsorption Y Y Y Y Sample collection: blood, feces and vaginal washes To analyze antibodies : - Serum IgG - Mucosal SIgA (faecaland vaginal) Humoral responseanalysis

  3. High IgG HIV-p24 titre in sera SerumIgG titre W0 W2 W4 W6 p24 PLA-p24 Chito +P24 p24+ Poly(I:C) PLA-p24 + Chito PLA-p24 + Poly(I:C) Chito-Poly(I:C) + p24 PLA-p24 + Chito-Poly(I:C) • PLA-p24 >> p24 alone. • The quickest and more efficient systemic immune response is observed with Chitosan-Poly(I:C) + p24.

  4. Mucosal immune responses Vaginal IgA W0 Vaginal IgG D.O. W2 W4 W6 D.O. p24 PLA-p24 Chito + p24 p24 + Poly(I:C) PLA-p24 + Poly(I:C) PLA-p24 + Chito Chito-Poly(I:C) + p24 PLA-p24 + Chito-Poly(I:C) p24 PLA-p24 Chito + p24 p24 + Poly(I:C) PLA-p24 + Chito-Poly(I:C) Chito-Poly(I:C) + p24 PLA-p24 + Poly(I:C) PLA-p24 + Chito • No specific induction of p24 immune responses in mucosal sites (vaginal and intestinal).

  5. Conclusions • Subcutaneous administration of NPs-p24 induce quick and high systemic immune response. • The quickest and more efficient systemic immune response is observed with Chitosan-Poly(I:C) + p24. • Subcutaneous administration does not induce mucosal immune response. • Results in mucosa could be explained by a non optimum dose of poly(I:C). • - Try with different doses of poly(I:C) • - Try with different adjuvant molecules (TLR-7, -8, NODs ligands,…) • Try other routes of administration: oral, vaginal, intranasal, … • Try a prime-boost strategy (combine with viral vectors). Adjunction of a co-stimulatory molecule TLR-3 agonist (poly(I:C)) with p24 co delivered by nanoparticles of chitosan amplify systemic immune response against p24.

  6. Acknowledgement

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