Interferon-gamma production by peripheral blood mononuclear cells from residents of an area endemic for Schistosoma mansoni.

During human schistosomiasis host responses to antigens of various parasite life-cycle stages may contribute to whether the severe, hepatosplenic state develops or the patient remains relatively asymptomatic throughout infection, and may play a role in resistance. This study evaluated production of interferon gamma (IFN-gamma) in vitro by schistosome antigen-stimulated peripheral blood mononuclear cells (PBMCs) from asymptomatic patients, and by PBMCs from apparently uninfected, untreated persons living in areas endemic for Schistosoma mansoni ('endemic normals'). IFN-gamma production parallels PBMC proliferation in that schistosomal egg antigens stimulate patent patients' cells poorly, but strongly stimulate PBMCs from 'endemic normals'. This is proportionally true for antigens from adult worms and cercariae. Although asymptomatic patent patients' cells produced little or no IFN-gamma in response to the 3 schistosomal antigenic extracts, their PBMCs, and PBMCs from 'endemic normals', produced expected amounts of IFN-gamma when exposed to phytohaemagglutinin. This implies that persons with patent infections have schistosome antigen-specific defects in their ability to respond to IFN-gamma production that are not exhibited by putatively resistant 'endemic normals'.

The human immune response to defined immunogens of Schistosoma mansoni: elevated antibody levels to paramyosin in stool-negative individuals from two endemic areas in Brazil.

Sera from individuals living in 2 areas endemic for Schistosoma mansoni in Minas Gerais, Brazil were assayed for the presence of antibodies against paramyosin and glutathione-S-transferase (GST), molecules previously implicated as vaccine immunogens from studies in laboratory hosts. A group was identified consisting of subjects who were stool-negative and had no record of previous infection but who were seropositive by enzyme-linked immunosorbent assay against crude adult worm antigen (SWAP). These individuals had anti-paramyosin antibody levels which were dramatically elevated with respect to those measured in infected (stool-positive) individuals living in the same endemic area. In contrast, the same 2 groups of stool-positive and stool-negative subjects could not be distinguished on the basis of their seroreactivity to either GST or SWAP. After chemotherapy, anti-paramyosin antibodies rose above pre-treatment levels and remained elevated in those individuals who became stool-negative. In contrast, anti-paramyosin antibodies decreased to pretreatment values in drug-treated individuals who failed to show complete parasitological cure. These results suggest that the immune response of humans to paramyosin may play a role in natural resistance to schistosome infection, and that an elevated antibody level against this antigen may be a useful correlate of drug-induced cure.

Prospects for a nonliving vaccine against schistosomiasis based on cell-mediated immune resistance mechanisms.

We have designed a vaccine model based on induction of cell-mediated immunity and shown that it protects mice against Schistosoma mansoni infection. Mice are immunized by intradermal injection with schistosome antigens plus BCG. Resistance is dependent on the route of antigen presentation and the adjuvant chosen. The pattern of resistance correlates with sensitization of T lymphocytes for production of gamma interferon, a macrophage activating lymphokine that stimulates the cellular effector mechanism of protection. Purified schistosome paramyosin, a muscle cell component present in soluble parasite antigenic preparations, is immunogenic for T lymphocytes and induces resistance when given intradermally with BCG. It is likely that this protein, and possibly other soluble molecules that are released by the parasites of a challenge infection, induce a cellular inflammatory response resulting in larval trapping and/or killing by activated macrophages. These results verify the feasibility of a vaccine against schistosomiasis based on induction of cell-mediated immune resistance mechanisms.