Efficient oral vaccination by bioengineering virus-like particles with protozoan surface proteins

SERRADELL MC; LUCÍA RUPIL; MARTINO RA; PRUCCA, CÉSAR G.; CARRANZA, PEDRO G.; ALICIA SAURA; ELMER A FERNÁNDEZ; PABLO R GARGANTINI; TENAGLIA, ALBANO H.; PETITI, JUAN P. ; REINOSO-VIZCAINO, NICOLÁS; ECHENIQUE, JOSÉ; BEROD L; PIAGGIO, ELIANE; BELLIER, BERTRAND; SPARWASSER T; KLATZMANN, DAVID; LUJAN HD

Ciudad Autónoma de Buenos Aires

Encuentro; Humboldt Colloquium. "Shaping the future of German-Argentinian Scientific Cooperation- The role of curiosity-driben Research; 2018

Alexander von Humboldt Foundation

Intestinal and free-living protozoa, such as Giardia lamblia, express a dense coat of variantspecificsurface proteins (VSPs) on trophozoites that protects the parasite inside the host?sintestine. Here we show that VSPs not only are resistant to proteolytic digestion and extremepH and temperatures but also stimulate host innate immune responses in a TLR-4 dependentmanner. We show that these properties can be exploited to both protect and adjuvantvaccine antigens for oral administration. Chimeric Virus-like Particles (VLPs) decorated withVSPs and expressing model surface antigens, such as influenza virus hemagglutinin (HA)and neuraminidase (NA), are protected from degradation and activate antigen presentingcells in vitro. Orally administered VSP-pseudotyped VLPs, but not plain VLPs, generate robustimmune responses that protect mice from influenza infection and HA-expressing tumors.This versatile vaccine platform has the attributes to meet the ultimate challenge of generatingsafe, stable and efficient oral vaccines.