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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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posted on 2023-05-19, 18:16 authored by Minigo, G, Katie FlanaganKatie Flanagan, Slattery, RM, Plebanski, M
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 off by 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.

History

Publication title

Frontiers in Immunology

Volume

8

Article number

115

Number

115

Pagination

1-9

ISSN

1664-3224

Department/School

Tasmanian School of Medicine

Publisher

Frontiers Research Foundation

Place of publication

Switzerland

Rights statement

Copyright 2017 Mingo, Flanagan, Slattery and Plebanski. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

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