A NOVEL STRATEGY FOR THE DEVELOPMENT OF A VACCINE AGAINST THE INTESTINAL PARASITE GIARDIA LAMBLIA

BORGOGNO, C; RÓPOLO, A; QUIROGA, R; RIAL, A; MALETTO, B; PISTORESI, MC; CHABALGOITY, JA; LUJAN, H.

Mendoza

Congreso; VII Congreso Argentino de Protoología y Enfermedades Parasitarias; 2005

Giardia lamblia causes diarrhea and intestinal upset, been one of the most common human parasites worldwide. Although numerous drugs are available, many of them shown high toxicity and newly drug-resistant parasites have been identifies. 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 entirely 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. We recently found that antigenic variation is regulates by a post-transcriptional gene silencing mechanisms (PTGS) and characterized the enzymes involved 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 in immunization protocols in the mouse model of Giardasis. Results indicated that oral as well as nasal immunization induced an antibody-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.