Mosaic and cocktail capsid-virus-like particle vaccines for induction of antibodies against the EPCR-binding CIDRα1 domain of PfEMP1

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Abstract

The sequestration of Plasmodium falciparum-infected erythrocytes to the host endothelium is central to the pathogenesis of malaria. The sequestration is mediated by the parasite´s diverse Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants, which bind select human receptors on the endothelium. Severe malaria is associated with PfEMP1 binding human endothelial protein C receptor (EPCR) via their CIDRα1 domains. Antibodies binding and inhibiting across the sequence diverse CIDRα1 domains are likely important in acquired immunity against severe malaria. In this study, we explored if immunization with AP205 bacteriophage capsid-virus-like particles (cVLPs) presenting a mosaic of diverse CIDRα1 protein variants would stimulate broadly reactive and inhibitory antibody responses in mice. Three different mosaic cVLP vaccines each composed of five CIDRα1 protein variants with varying degrees of sequence conservation of residues at and near the EPCR binding site, were tested. All mosaic cVLP vaccines induced functional antibodies comparable to those induced by matched cocktails of cVLPs decorated with the single CIDRα1 variant. No broadly reactive responses were observed. However, the vaccines did induce some cross-reactivity and inhibition within the CIDRα1 subclasses included in the vaccines, demonstrating potential use of the cVLP vaccine platform for the design of multivalent vaccines.

Original languageEnglish
Article numbere0302243
JournalPLoS ONE
Volume19
Issue number7
Number of pages13
ISSN1932-6203
DOIs
Publication statusPublished - 2024

Bibliographical note

Copyright: © 2024 Riedmiller et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Keywords

  • Animals
  • Protozoan Proteins/immunology
  • Mice
  • Vaccines, Virus-Like Particle/immunology
  • Humans
  • Endothelial Protein C Receptor/immunology
  • Malaria Vaccines/immunology
  • Plasmodium falciparum/immunology
  • Antibodies, Protozoan/immunology
  • Female
  • Protein Domains
  • Protein Binding
  • Mice, Inbred BALB C
  • Receptors, Cell Surface/immunology
  • Malaria, Falciparum/prevention & control

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