ACTIVATION OF DENDRITIC CELLS BY GIARDIA VARIANT-SPECIFIC SURFACE PROTEINS (VSP) AND VSP-PSEUDOTYPED VIRUS-LIKE PARTICLES

RUPIL, LUCÍA; SERRADELL, MARIANELA; MARTINO, ROMÁN; GARGANTINI, PABLO; LUJÁN, HUGO

Buenos Aires

Congreso; XXVII Reunión Anual - SAP; 2015

Sociedad Argentina de Protozoología

It has been shown that Giardia lamblia variable surface antigens (VSPs) have a remarkable intrinsic immunogenicity and are capable to resist the harsh conditions of the gastrointestinal tract. In addition, significant progress has been made regarding the use of vaccines composed of Virus-like Particles (VLPs), indicating the strong capability of particulate vaccines to enhance systemic immune responses. Our hypothesis is that an efficient oral vaccine platform can be generated by combining the benefits of Giardia VSPs as protective agents with the advantages of VLPs as efficient immunogens. We therefore developed fluorescent VSP-enveloped VLPs (pseudotyping) for oral immunization of heterologous antigens (oVLPs). Since dendritic cells (DCs) are the main players between the innate and the adaptive immunity and are required for initiation of T cell-mediated responses, their interaction with VSPs and oVLPs was evaluated. Bone marrow DCs from C57Bl/6 mice were stimulated with either recombinant VSP1267, naked (nVLPs) or VSP1267-pseudotyped oVLPs. Expression of different cell activation parameters, such as CD40, CD86, many cytokines and nitric oxide production were tested. When oVLPs and nVLPs were compared, the VSP-pseudotyped VLPs showed an increased stimulatory capacity, with higher levels in expression of co-stimulatory molecules, enhanced production of IL-4, IL-6, IL-10, TNF and nitric oxide, as well as a higher VLP uptake, indicating that the presence of VSP improved VLP immunogenicity. In turn, VSP1267 alone was also able to increase CD40 and CD86 levels, but only induced a slight increase of TNF. Thus, although VSPs show immunostimulating properties, these capabilities were strongly improved when these proteins were covering the VLPs. Further characterization of VSPs and oVLPs will contribute to the use of these molecules as mucosal adjuvants for the production of vaccines to be administered orally.