RAPID ONSET OF MALARIA-INDUCED MORTALITY BY IMMUNIZATIONS WITH LIPO-PEPTIDES - AN EXPERIMENTAL-MODEL TO STUDY DELETERIOUS IMMUNE-RESPONSES AND IMMUNOPATHOLOGY IN MALARIA

We have recently shown that circumsporozoite (CS) protein-based cytoto xic T-cell epitope of Plasmodium berghei coupled to monopalmitic and t ripalmitic acid was able to induce cytotoxic T-cell responses. In the present study, we investigated whether lipopeptide derivatized CS prot ein B and T helper epitopes in different combinations will be able to induce protective immune responses against sporozite challenge. Severa l P. berghei CS peptides with monopalmitic fatty acid tails were prepa red, suspended in an oil-in-water with monopalmitic fatty acid tails w ere prepared, suspended in an oil-in-water emulsion, and used to immun ize and boost female A/J mice. The mice were challenged iv. with viabl e sporozoites of P. berghei (ANKA) two weeks after the last immunizati on. While immunization with some of these vaccine formulations induced protective immune responses, others shifted the typical bimodal patte rn of P. berghei sporozoite induced death toward a rapid onset of deat h in a peptide specific manner. Therefore, demonstration that immuniza tion with formulations of malarial peptides can cause enhanced malaria -related death provides an experimental model to delineate characteris tics of deleterious immune responses. Copyright (C) 1997 Published by Elsevier Science Ltd.