Experimental animal models in vaccination against schistosomiasis.
Contrary to previous expectations, innate resistance to a primary schistosome infection is mediated predominantly in the lungs of many laboratory rodents. In addition, the phenomenon of non-permissiveness seen in a sub population of 129 strain mice, is associated with worm relocation from the liver to the lungs and is facilitated by dramatic alteration to the lung and liver vasculature; lung located adult worms exhibit gut damage and are ultimately destroyed within eosinophil-rich inflammatory focal reactions. It is now clear that the immunity induced by exposure to radiation-attenuated cercariae can be affected in the skin (mice), the lungs (mice and rats) or the liver (guinea pigs) of laboratory rodents. Moreover, the fact that skin phase resistances involves radio-sensitive cells, while lung and liver phase immunity centres on radio-resistant leucocytes, resolves current discord in the literature. Immobilisation and trapping of challenge larvae within focal inflammatory infiltrates is nevertheless common to both skin and lung phase attrition. Hyperimmunisation of rodents with irradiated cercariae is associated with a switch in immunoglobulin isotype and serum harvested from such donors is able to protect naive recipients passively; transferred serum recruits effector cells. Challenge parasites exhibit a broader window of sensitivity to vaccine immunity than was originally envisaged; stages ranging from the 3 to 4 day old skin/lung stage larva to the 3 week old juvenile liver worm constitute targets of protective resistance in vivo. This is at variance with the fact that newly transformed schistosomula constituting the primary targets of in vitro effector mechanisms, a feature perhaps related to our inability to mimic the process of intravascular parasite immobilisation and trapping in the test tube. Finally, schistosomicidal drugs such as Praziquantel can, by re-exposing disguised parasite antigens, facilitate the expression of vaccine immunity in sites additional to those at which resistance is normally mediated.
McLaren
D J
DJ
Division of Parasitology, National Institute for Medical Research, Mill Hill, London, UK.
D000818:Animals; D006168:Guinea Pigs; D007110:Immunity, Active; D007113:Immunity, Innate / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000469:parasitology; D008168:Lung / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008954:Models, Biological; D011223:Praziquantel / Q000627:therapeutic use; D051381:Rats; D012550:Schistosoma mansoni / Q000254:growth & development / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000188:drug therapy / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D012867:Skin / Q000276:immunology / Q000469:parasitology; D014612:Vaccines / Q000276:immunology*
D014612:Vaccines; D011223:Praziquantel