MUCOSAL VACCINATION AGAINST SCHISTOSOMIASIS USING LIPOSOME-ASSOCIATEDSM-28 KDA GLUTATHIONE-S-TRANSFERASE

A variety of experimental models have shown that immunization using th e glutathione S-transferase from Schistosoma mansoni (Sm28GST) can ind uce protective immunity against this parasite. This immunity has been related to the production of Th2 type antibodies against the antigen i n both mice and humans. The work presented in this paper describes the development of a mucosal immunization protocol using liposomes which is designed to promote production of specific antibodies of isotypes r elated to a Th2 immune response. The liposomes were multilamellar and composed of various synthetic phospholipid mixtures. The liposome vect or was used to convey the Sm28GST antigen to gut associated lymphoid t issue. The association of the Sm28GST antigen with liposomes containin g different lipid mixtures was initially studied The degree of interac tion of the antigen was found to increase with the hydrocarbon chain l ength of the lipids used. It was demonstrated that the protein was pre sent on both the inner and the outer membranes of the liposome vesicle s. It was also shown that the major epitopes of Sm28GST were accessibl e to specific antibodies, confirming a conservation of its main antige nic features. Additionally, enzymatic activity of the protein/liposome complex was also demonstrated indicating a conservation of the tertia ry structure of the protein. An optimal Sm28GST/ liposome complex was established and administered orally to mice. This treatment resulted i n both a mucosal and systemic immune response to the antigen Sm28GST. This was demonstrated by the detection of specific IgA in gut washes a nd specific IgGl, IgG2b in sera. Immunization by Sm28GST/liposome comp lex followed by challenge with parasite showed that Sm28GST given oral ly in these conditions bore protective activity. This last result open s the possibility of mucosal vaccination against schistosomiasis. Copy right (C) 1996 Elsevier Science Ltd.