title: Rapid onset of malaria-induced mortality by immunizations with lipo-peptides: an experimental model to study deleterious immune responses and immunopathology in malaria.
abstract: We have recently shown that circumsporozoite (CS) protein-based cytotoxic T-cell epitope of Plasmodium berghei coupled to monoplamitic and tripalmitic acid was able to induce cytotoxic T-cell responses. In the present study, we investigated whether lipopeptide derivatized CS protein B and T helper epitopes in different combinations will be able to induce protective immune responses against sporozoite challenge. Several P. berghei CS peptides with monopalmitic fatty acid tails were prepared, suspended in an oil-in-water emulsion, and used to immunize and boost female A/J mice. The mice were challenged iv. with viable sporozoites of P. berghei (ANKA) two weeks after the last immunization. While immunization with some of these vaccine formulations induced protective immune responses, others shifted the typical bimodal pattern of P. berghei sporozoite induced death toward a rapid onset of death in a peptide specific manner. Therefore, demonstration that immunization with formulations of malarial peptides can cause enhanced malaria-related death provides an experimental model to delineate characteristics of deleterious immune responses.
authors.affiliation: National Center for Infectious Diseases, Centers for Disease Control and Prevention, U.S. Department of Public Health and Human Service, Atlanta, GA 30033, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Reed
authors.forename: A F
authors.initials: AF
authors.lastname: Verhuel
authors.forename: R L
authors.initials: RL
authors.lastname: Hunter
authors.forename: V
authors.initials: V
authors.lastname: Udhayakumar
authors.forename: V
authors.initials: V
authors.lastname: Louis-Wileman
authors.forename: V J
authors.initials: VJ
authors.lastname: Jennings
authors.forename: D L
authors.initials: DL
authors.lastname: Jue
authors.forename: R M
authors.initials: RM
authors.lastname: Wohlhueter
authors.forename: A A
authors.initials: AA
authors.lastname: Lal
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D008074:Lipoproteins / Q000737:chemistry; D008288:Malaria / Q000276:immunology* / Q000401:mortality* / Q000473:pathology; D017780:Malaria Vaccines / Q000009:adverse effects* / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage*; D010962:Plasmodium berghei / Q000276:immunology; D015800:Protozoan Proteins / Q000737:chemistry
chemical_list: D008074:Lipoproteins; D017780:Malaria Vaccines; D010455:Peptides; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan