Mucosal vaccination against schistosomiasis using liposome-associated Sm 28 kDa glutathione S-transferase

A variety of experimental models have shown that immunization using the glutathione S-transferase from Schistosoma mansoni (Sm28GST) can induce protective immunity against this parasite. This immunity has been related to the production of Th2 type antibodies against the antigen in 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 related to a Th2 immune response. The liposomes were multilamellar and composed of various synthetic phospholipid mixtures. The liposome vector was used to convey the Sm28GST antigen to gut associated lymphoid tissue. The association of the Sm28GST antigen with liposomes containing different lipid mixtures was initially studied. The degree of interaction of the antigen was found to increase with the hydrocarbon chain length of the lipids used. It was demonstrated that the protein was present on both the inner and the outer membranes of the liposome vesicles. It was also shown that the major epitopes of Sm28GST were accessible to specific antibodies, confirming a conservation of its main antigenic features. Additionally, enzymatic activity of the protein/liposome complex was also demonstrated, indicating a conservation of the tertiary structure of the protein. An optimal Sm28GST/ liposome complex was established and administered orally to mice. This treatment resulted in both a mucosal and systemic immune response to the antigen Sm28GST. This was demonstrated by the detection of specific IgA in gut washes and specific IgG1, IgG2b in sera. Immunization by Sm28GST/liposome complex followed by challenge with parasite showed that Sm28GST given orally in these conditions bore protective activity. This last result opens the possibility of mucosal vaccination against schistosomiasis.