CENTRO DE INVESTIGACION Y DESARROLLO EN INMUNOLOGIA Y ENFERMEDADES INFECCIOSAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Activation of Dendritic Cells by Giardia lamblia recombinant Variant-specific Surface Proteins (VSPs) and VSP-pseudotyped virus-like particles (VLP)
RUPIL LUCÍA LARA; SERRADELL MARIANELA C; MARTINO ROMAN A; GARGANTINI PABLO RUBÉN; LUJAN HUGO D
Congreso; XXVII Reunión Anual de la Sociedad Argentina de Protozoología; 2015
It has recently been shown that VSP have a remarkable immunogenicity per se, they are able to bind to the intestinal mucosa and resist the adverse conditions of the gastrointestinal tract. On the other hand, significant progress has been made in recent years regarding use of vaccines composed of virus-like particles, showing its strong ability in enhancing immune response. Our hypothesis is that efficient oral vaccines can be generated by combining the benefits of Giardia VSP as protective agents with the advantages of VLP as efficient carriers of antigens, which led us to develop VSP-pseudotyped VLPs (VLPVSP). Being dendritic cells the main cells that act as messengers between the innate and adaptive immunity and are required for the initiation of T-cell responses, their interaction with VSPs and VLP-VSP was evaluated. BMDCs from C57Bl/6 mouse were stimulated with recombinant VSP1267 produced in an insect expression system and VLP-VSP1267-GFP VLP-GFP (without VSP as control) produced in HEK cells. Expression of different activation cell parameters such as CD40, CD86, many cytokines and nitric oxide production were tested. When VLP-VSP1267-GFP and VLP-GFP were compared, the VSP-pseudotyped VLP showed an increased stimulating capacity, with higher levels of expression of co-stimulatory molecules, more production of IL-4, IL-6, IL-10, TNF and nitric oxide, as well as a higher VLP uptake (GFP measurement); indicating that the presence of VSP improved VLP immunogenicity. In turn, VSP1267 alone was also able to increase the CD40 and CD86 levels in BMDCs, but only induced a slight increase of TNF. Thus, although VSPs show immunostimulating properties, they were exponentially raised when these proteins were covering VLP. The characterization of immunogenic properties of both VSPs as VLP-VSP will contribute to knowledge of these molecules as potential mucosal adjuvants.