IMMUNOGENIC PROPERTIES OF THE EXTRACELLULAR DOMAIN OF VARIANT SURFACE PROTEINS OF Giardia lamblia

SERRADELL MARIANELA C; MARTINO ROMAN; RUPIL LUCIA L.; MARTINA MARIANA A; PERALTA DAMIAN O; LUJAN HUGO DANIEL

Córdoba

Congreso; LII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2016

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

The human parasite G. lamblia is covered by a tight coat comprised Variant-specific Surface Proteins (VSPs). Previous results showed that oral immunization with purified native VSPs, without adjuvants, elicited a protective immune response against challenges with the parasite in gerbils, dogs and cats. To further study the immunogenic properties of VSPs, the extracellular, cysteine-rich domain of three different VSPs was produced in an insect cell expression system, which yields proteins with correct disulfide bonds, in serum free medium, in absence of pyrogen and with high purity. To determine if these ΔVSPs are able to activate receptors of the immune system we used a reporter cell system. When a broad panel of human TLR genes was used for screening, we found that ΔVSP1267 was able to signal though TLR2 and TLR4. Subsequent studies with mouse receptors demonstrated that this activation was dose-dependent and that it was stronger in mTLR4 than in mTLR2. Similar results were obtained with ΔVSPH7 and ΔVSP9B10. In vitro, these proteins showed activation of macrophages and dendritic cells, inducing up regulation of co-stimulatory molecules. These results indicate that the immunogenic properties of Giardia VSPs are related to their ability to activate the innate immune system. Since these molecules have also protective activity, VSPs can be used in the formulation of oral vaccines