Vaccination against severe hepatosplenic disease in schistosomiasis japonica: a hypothesis

ABSTRACT

Manifestations of serious disease in chronic schistosomiasis such as portal hypertension, collateral circulation and hepatosplenomegaly are ascribed to T cell-dependent obstructive granuloma formation with subsequent fibrosis principally in the liver. Collagen synthesis and tissue fibrosis may also result from indirect effects of T cell dependent macrophage activation but also from direct effects of eggs productions. Mature eggs are known to be a rich source of "immunopathologic" antigens. It is proposed that antibodies, through their effects on both mature and immature eggs, may markedly decrease opportunities for expression of immunopathologic responses. The hypothesis is that antibodies of certain specificities and certain istotypes can inhibit embryonation of immature and/or effect early or accelerated destruction of mature eggs. The disease modulating consequences of these stem from inhibition of sustained production and release of immunopathologic antigens. The anti-immunopathologic effects being termed "anti-embryonation immunity" (directed against immature eggs) and "anti-miracidial immunity" (accelerated desctruction of mature eggs). On theoretical grounds, sensitization of hosts for anti-embryonation immunity would be a particularly effective means of vaccinating against severe hepatosplenic disease. Such a vaccination strategy could also lead to reduced transmission of infection. It should also inhibit production of egg products with effects in the liver such as hepatotoxicity and promotion of collagen synthesis. The hypothesis emphasizes the consequences of the immune responses on the source of immunopathologic antigens (i.e the egg) in modulation of granuloma formation and disease abatement. The alternative, and in our view, less attractive strategy of vaccination for anti-immunopathology, is to promote immuregulatory responses (e.g. suppressor T cells) which operate to inhibit immunopathologic effector cells and antibodies.(Summary)