Polymorphism in liver-stage malaria vaccine candidate proteins: Immune evasion and implications for vaccine design

Katie L. Flanagan, Kirsty L. Wilson, Magdalena Plebanski

Research output: Contribution to journalReview ArticleResearchpeer-review

14 Citations (Scopus)

Abstract

The pre-erythrocytic stage of infection by malaria parasites represents a key target for vaccines that aim to eradicate malaria. Two important broad immune evasion strategies that can interfere with vaccine efficacy include the induction of dendritic cell (DC) dysfunction and regulatory T cells (Tregs) by blood-stage malaria parasites, leading to inefficient priming of T cells targeting liver-stage infections. The parasite also uses surgical strike strategies, whereby polymorphism in pre-erythrocytic antigens can interfere with host immunity. Specifically, we review how even single amino acid changes in T cell epitopes can lead to loss of binding to major histocompatibility complex (MHC), lack of cross-reactivity, or antagonism and immune interference, where simultaneous or sequential stimulation with related variants of the same T cell epitope can cause T cell anergy or the conversion of effector to immunosuppressive T cell phenotypes.

Original languageEnglish
Pages (from-to)389-399
Number of pages11
JournalExpert Review of Vaccines
Volume15
Issue number3
DOIs
Publication statusPublished - 3 Mar 2016

Keywords

  • antagonism
  • antigen
  • cross-reactivity
  • immune evasion
  • immune interference
  • Malaria
  • polymorphism
  • pre-erythrocytic
  • vaccine

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