info:eu-repo/semantics/article
Efficient oral vaccination by bioengineering virus-like particles with protozoan surface proteins
Fecha
2019-12Registro en:
Serradell, Marianela del Carmen.; Rupil, Lucia; Martino, Román Alejandro; Prucca, Cesar German; Carranza, Pedro Gabriel; et al.; Efficient oral vaccination by bioengineering virus-like particles with protozoan surface proteins; Nature; Nature Communications; 10; 1; 12-2019; 361-380
2041-1723
CONICET Digital
CONICET
Autor
Serradell, Marianela del Carmen.
Rupil, Lucia
Martino, Román Alejandro
Prucca, Cesar German
Carranza, Pedro Gabriel
Saura, Alicia
Fernandez, Elmer Andres
Gargantini, Pablo Ruben
Tenaglia, Albano Heraldo
Petiti, Juan Pablo
Tonelli, Renata R.
Reinoso Vizcaino, Nicolas Martin
Echenique, Jose Ricardo
Berod, Luciana
Piaggio, Eliane
Bellier, Bertrand
Sparwasser, Tim
Klatzmann, David
Lujan, Hugo Daniel
Resumen
Intestinal and free-living protozoa, such as Giardia lamblia, express a dense coat of variant-specific surface proteins (VSPs) on 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 a TLR-4 dependent manner. We show that these properties can be exploited to both protect and adjuvant vaccine antigens for oral administration. Chimeric Virus-like Particles (VLPs) decorated with VSPs and expressing model surface 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 infection and HA-expressing tumors. This versatile vaccine platform has the attributes to meet the ultimate challenge of generating safe, stable and efficient oral vaccines.