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; LUJÁN, HD

Mendoza, Argentina

Congreso; VII Congreso Argentino de Protozoología y Enfermedades Parasitarias.; 2005

Giardia lamblia causes diarrea and intestinal upset, and has been considered 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 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 switches the expression of its VSPs allowing the parasite to evade the host´s inmune system and to cause chronic and persistant infections. We recently found that antigenic variation is regulated by a post-transcriptional gene silencing mechanism (PTGS) and characterized the enzymes involved in this process. We understod that by knocking down the expression of RNA dependant RNA polymerase (RdRP) or Dicer in G. lamblia trophozoites, these cells would express the entire repertory of VSPs. Interestingly, results show that trophozoites lacking a functional PTGS mechanism do not undergo antigenic variation. These cells, in addition to different recombinant VSPs from G. muris and G. lamblia, are being used in inmunization protocols in the mouse model of Giardiasis. Results indicate that oral as well as nasal inmunization induced an antibody-specific inmune response in mice. Further studies using this system will facilitate the development of anti-Giardia vaccines to be used in humans and domestic animals.