Novel oral vaccine based on the full repertoire of Giardia VSPs prevents establishment of infection and reduces chronic giardiasis in domestics animals

SERRADELL MARIANELA C; SAURA ALICIA; RUPIL LUCÍA LARA; GARGANTINI PABLO RUBÉN; FAYA MARCELA; FURLAN PAULINA; LUJAN HUGO D

Congreso; XXVII Reunión Científica Anual de la Sociedad Argentina de Protozoología; 2015

Sociedad Argentina de Protozoología

Giardia lamblia is an intestinal parasite of humans and one of the most common enteric pathogen of domestic animals, including cats, dogs, and cattle. Clinical manifestations of giardiasis, such as chronic or acute diarrhea, anorexia, weight loss, and lethargy, have been associated with Giardia infections in both domestic and farm animals. A few anti-parasitic drugs are routinely used to treat giardiasis, but re-infections are common and drug resistant strains have already been reported. Unfortunately, efficient vaccines against Giardia are not available. Giardia undergoes antigenic variation, a mechanism that allows parasites to evade the host´s immune response, producing chronic and/or recurrent infections. Antigenic variation is characterized by the continuous switching in expression of a family of homologous genes encoding surface antigens. We have previously found that the mechanism controlling variant-specific surface proteins (VSPs) switching in Giardia involves components of the RNA interference (RNAi) pathway. Only one VSP, from a repertoire of ~200 VSP genes, is expressed on the surface of individual trophozoites; however, disruption of the RNAi machinery generates trophozoites expressing the entire repertoire of VSPs. We have also showed that oral immunization of gerbils with VSPs isolated from these altered parasites shows high levels of protection, clearly indicating that targeting the entire repertoire of surface antigenic variants is an effective approach to prevent infections. Here, we tested this vaccine in cats and dogs, demonstrating that the vaccine is highly efficient in preventing new infections and reducing chronic giardiasis in domestic animals both in experimental and natural infections. Remarkably, immunization of dogs in a highly endemic area strongly decreased the percentage of infected children in the community, suggesting that this vaccine blocks the zoonotic transmission of the disease.