MUNA: MULTIEFFECTOR NANOVESICLES AS POTENT READY TO USE VACCINE ADJUVANTS AGAINST NEGLECTED DISEASES.

CAIMI, AYELÉN T.; PETRAY, PATRICIA B; CARGNELUTTI, DIEGO E.; ROMERO, EDER L; FEDERICO PARRA; VERMEULEN, MÓNICA

Mar del Plata

Congreso; Congreso SAIC-SAI-SAFE; 2016

SAI

Chagas and leishmaniasis, two neglected diseases caused bythe protozoans Trypanosoma cruzi and Leishmania sp. respectively,affect more than 8 million people of populations living in povertyand without adequate sanitation. Currently, the development ofeffective vaccines is still an outstanding bill and adjuvants are thekey elements to stimulate and potentiate the immune response.In this work, imiquimod (IMQ), a Toll Like Receptor 7 (TLR7)ligand, was incorporated into archaeosomes (ARC), nanovesiclesmade of archaeolipids that contain ligands of scavenger receptors.The fundamentals underlying this design are that ARC will begreedily recognised and endocyted by antigen presenting cells incomparison with conventional liposomes and the IMQ will accessin a greater quantity to the endosomal TLR7 causing a strongerimmune response. Furthermore, the capacity of ARC with IMQ(ARC-IMQ) to act as vaccine adjuvants against L. amazonensisand T. cruzi was tested in vivo in mice models. In one experiment,formulations of ARC-IMQ, ARC and IMQ alone and Montanide ISA763 (a commercial adjuvant approved for animal?s vaccines butnot humans) were mixed with total leishmania antigen and admin -istrated subcutaneously in Balb/c mice three times, one every 15days. In other experiment, the same immunization protocol wastested in C3H mice but the formulations administrated were ARCIMQand IMQ alone mixed with total homogenate of T. cruzi (TH),ARC-IMQ and TH free. On day 35, the humoral immune responseinduced by each formulation was evaluated. Finally, four weeksafter the last administration the immune cell populations wereanalysed by flow cytometry.The results demonstrate that ARC-IMQ can elicit better antigenspecific IgG antibody response in comparison with ARC or IMQalone and with Montanide and more activation of CD4, CD8 andB lymphocytes than ARC.In conclusion, despite further preclinic investigation is neededto understand the mechanism of action, ARC-IMQ could be usedas vaccine adjuvants against neglected diseases.