A novel strategy for the development of a vaccine against the intestinal parasite Giardia lamblia

CARMEN BORGOGNO; ANDREA RÓPOLO; RODRIGO QUIROGA; RIAL A; BELKIS MALETTO; MARIA CRISTINA PISTORESI; ALEJANDRO CHABALGOITY; HUGO DANIEL LUJÁN

Mendoza - Argentina

Congreso; VII Congreso Argentino De Protozoología y Enfermedades Parasitarias; 2005

Sociedad Argentina de Protozoología

Giardia lamblia, causes diarrhea and intestinal upset, is one of the most common human parasites worldwide. Although numerous drugs are available, many of them have shown high toxicity and newly drug-resistant parasites have been identified. The aim of this study was to develop new strategies for the design of an experimental vaccine against this parasite. The surface of G. lamblia is enterely covered by highly antigenic variant specific surface proteins (VSPs). Trophozoites express a unique VSP on their surface but they are able to undergo antigenic variation, a process by which Giardia switch the expression of its VSPs allowing the parasite to evade the host?s immune response and to cause chronic and persistent infections. In endemic areas, individuals lack clinical manifestations of the disease due to the fact that they have been ?naturally vaccinated? during their life. We recently found that antigenic variation is regulated by a post-transcriptional gene silencing mechanims (PTGS) and characterized the enzymes envolved in this process (RNA-dependent RNA polymerase ?RdRP- and Dicer). We understood that by knocking-down the expression of RdRP or Dicer in G. lamblia trophozoites, these cells will be able to express the entire repertory of VSP. Interestingly, results showed that trophozoites lacking a functional PTGS mechanism do not undergo antigenic variation. These cells, in addition to different recombinant VSPs from both G. lamblia and G. muris are being used different immunization protocols in the mouse model of Giardiasis. Results indicated that oral as well as nasal immunization induced an antobody-specific immune response in mice. Further studies using this system will facilitate the development of anti-Giardia vaccine to be used in human and domestic animals.