June 6-11, 2010
The incorporation of antigens into poly-methyl vinyl ether-co-maleic anhydride nanoparticles (NP) has demonstrated to enhance the immune responses in terms of a potent Th1-adjuvant capacity. This fact may be explained by the implemented possibilities that NP render to the antigen: controlled release from the vehicle and chemotaxis for APC recruitment. Besides, after oral administration, it was reported that the bioadhesive nature of the polymer enhanced the interaction of the particulate-adjuvant to the gut mucosa. Moreover, these NP allow the adhesion of antigens and ligands to its outer shell, creating high antigen density surfaces that increase the possibilities of antigen recognition and/or capture by the APCs. Taken together, from the ability of NP to induce potent immune responses our hypothesis was that NP are able to trigger determined elements of the immune system. Explicitly, due to their particulate nature, NPs would interact with APCs, specifically DCs, through PRRs, including TLR. Our results revealed that poly(anhydride) NPs act as agonists of various TLRs (2, 4 and 5), triggering a Th1 profile cytokine release (IFN-γ: 478 pg/mL; IL12: 40 pg/mL) and, after incubation with dendritic cells, induce a 2.5 to 3.5 fold increase of CD54 and CD86 costimulatory molecule expression. Furthermore, in vivo studies suggest that NPs actively elicit a CD8+ T cell response. Taken together our results provide a better understanding of how NPs act as active Th1 adjuvants in immunoprophylaxis and immunotherapy through TLR exploitation. Acknowledgements This work was supported by grants from the Instituto de Salud Carlos III - FIS (PI070326) in Spain. References Arbos P, Wirth M, Arangoa MA, Gabor F, Irache JM. Gantrez AN as a new polymer for the preparation of ligand-nanoparticle conjugates. J Control Release 2002;83(3):321-30. Gomez S, Gamazo C, Roman BS, Ferrer M, Sanz ML, Irache JM. Gantrez AN nanoparticles as an adjuvant for oral immunotherapy with allergens. Vaccine 2007;25(29):5263-71. Irache JM, Salman HH, Gomez S, Espuelas S, Gamazo C. Poly(anhydride) nanoparticles as adjuvants for mucosal vaccination. Frontiers in Bioscience 2009. Ochoa J, Irache JM, Tamayo I, Walz A, DelVecchio VG, Gamazo C. Protective immunity of biodegradable nanoparticle-based vaccine against an experimental challenge with Salmonella Enteritidis in mice. Vaccine 2007;25(22):4410-9. Salman HH, Irache JM, Gamazo C. Immunoadjuvant capacity of flagellin and mannosamine-coated poly(anhydride) nanoparticles in oral vaccination. Vaccine 2009;27(35):4784-90.
Carlos Gamazo, Ibai Tamayo, and Ana I. Camacho, "POLY-METHYL VINYL ETHER-CO-MALEIC ANHYDRIDE NANOPARTICLES AS ANTIGEN DELIVERY AND ACTIVATING SYSTEMS" in "Vaccine Technology III", John G. Auniņš,Merck, USA; Barry C. Buckland, BiologicB, USA; Kathrin U. Jansen, Pfizer, USA; Paula Marques Alves, IBET, Portugal Eds, ECI Symposium Series, (2010). http://dc.engconfintl.org/vaccine_iii/30