Vaccination with altered peptide ligands of a Plasmodium berghei circumsporozoite protein CD8 T-cell epitope: A model to generate T cells resistant to immune interference by polymorphic epitopes

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Abstract

Many pathogens, including the malaria parasite Plasmodium falciparum, display high levels of polymorphism within T-cell epitope regions of proteins associated with protective immunity. The T-cell epitope variants are often non-cross-reactive. Herein, we show in a murine model, which modifies a protective CD8 T-cell epitope from the circumsporozoite protein (CS) of Plasmodium berghei (SYIPSAEKI), that simultaneous or sequential co-stimulation with two of its putative similarly non-cross-reactive altered peptide ligand (APL) epitopes (SYIPSAEDI or SYIPSAEAI) has radically different effects on immunity. Hence, co-immunization or sequential stimulation in vivo of SYIPSAEKI with its APL antagonist SYIPSAEDI decreases immunity to both epitopes. By contrast, co-immunization with SYIPSAEAI has no apparent initial effect, but it renders the immune response to SYIPSAEKI resistant to being turned offby subsequent immunization with SYIPSAEDI. These results suggest a novel strategy for vaccines that target polymorphic epitopes potentially capable of mutual immune interference in the field, by initiating an immune response by co-immunization with the desired index epitope, together with a carefully selected "potentiator" APL peptide.

Original languageEnglish
Article number115
JournalFrontiers in Immunology
Volume8
Issue numberFEB
DOIs
Publication statusPublished - 14 Feb 2017

Keywords

  • Altered peptide ligand
  • Antagonism
  • Cross-reactivity
  • Dendritic cell
  • Malaria
  • Plasmodium
  • T cell
  • Vaccine

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