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

MARTINO ROMAN A; SAURA, ALICIA; SERRADELL MARIANELA C; TENAGLIA ALBANO; PRUCCA CESAR; FERNANDEZ ELMER; REINOSO, NICOLÁS; PETITI, JUAN P; PIAGGIO ELIANE; ECHEÑIQUE, JOSÉ; KLATZMANN DAVID; BERTRAND BELLIER; LUJAN HUGO D; RUPIL LUCÍA LARA; CARRANZA PEDRO; GARGANTINI PABLO RUBÉN; TONELLI, RENATA; BEROD LUCIANA; SPARWASSER TIM

Buenos Aires

Workshop; Humboldt Colloquium: Shaping the Future of German-Argentinian Scientific Cooperation; 2018

The Alexander von Humboldt Foundation

Intestinal and free-living protozoa express surface proteins containing multiple CXXC motifs, where C is cysteine and X is any other amino acid. CXXC-rich Variant-specific Surface Proteins (VSPs) of Giardia lamblia form a dense coat on the entire surface of trophozoites that protects the parasite inside the host´s intestine. Here we show that VSPs not only are resistant to proteolytic digestion and extreme pH and temperatures, but also stimulate host innate immune responses in TLR-4 dependent manner. We tested whether these properties could be exploited to both protect and adjuvant vaccinal antigens for oral administration. We found that chimeric Virus-like Particles (VLPs) decorated with VSPs and expressing model antigens, such as Influenza virus hemagglutinin (HA) and neuraminidase (NA), are protected from degradation and activate antigen presenting cells in vitro. Orally administered VSP-pseudotyped VLPs, but not plain VLPs, generate robust immune responses that protect mice from Influenza infections and HA-expressing tumors. This versatile vaccine platform has the attributes to meet the ultimate challenge of generating safe, stable and efficient oral vaccines.