Mosaic and cocktail capsid-virus-like particle vaccines for induction of antibodies against the EPCR-binding CIDRα1 domain of PfEMP1
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Mosaic and cocktail capsid-virus-like particle vaccines for induction of antibodies against the EPCR-binding CIDRα1 domain of PfEMP1. / Riedmiller, Ilary; Fougeroux, Cyrielle; Jensen, Rasmus W; Kana, Ikhlaq H; Sander, Adam F; Theander, Thor G; Lavstsen, Thomas; Turner, Louise.
I: PLoS ONE, Bind 19, Nr. 7, 2024, s. e0302243.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Mosaic and cocktail capsid-virus-like particle vaccines for induction of antibodies against the EPCR-binding CIDRα1 domain of PfEMP1
AU - Riedmiller, Ilary
AU - Fougeroux, Cyrielle
AU - Jensen, Rasmus W
AU - Kana, Ikhlaq H
AU - Sander, Adam F
AU - Theander, Thor G
AU - Lavstsen, Thomas
AU - Turner, Louise
N1 - 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.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Animals
KW - Protozoan Proteins/immunology
KW - Mice
KW - Vaccines, Virus-Like Particle/immunology
KW - Humans
KW - Endothelial Protein C Receptor/immunology
KW - Malaria Vaccines/immunology
KW - Plasmodium falciparum/immunology
KW - Antibodies, Protozoan/immunology
KW - Female
KW - Protein Domains
KW - Protein Binding
KW - Mice, Inbred BALB C
KW - Receptors, Cell Surface/immunology
KW - Malaria, Falciparum/prevention & control
U2 - 10.1371/journal.pone.0302243
DO - 10.1371/journal.pone.0302243
M3 - Journal article
C2 - 39046960
VL - 19
SP - e0302243
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 7
ER -
ID: 400115992