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

Autor: Riedmiller I; Department of Immunology and Microbiology, Centre for translational Medicine and Parasitology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Fougeroux C; AdaptVac Aps, Copenhagen N, Denmark., Jensen RW; Department of Immunology and Microbiology, Centre for translational Medicine and Parasitology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Kana IH; Department of Immunology and Microbiology, Centre for translational Medicine and Parasitology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Sander AF; AdaptVac Aps, Copenhagen N, Denmark., Theander TG; Department of Immunology and Microbiology, Centre for translational Medicine and Parasitology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Lavstsen T; Department of Immunology and Microbiology, Centre for translational Medicine and Parasitology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Turner L; Department of Immunology and Microbiology, Centre for translational Medicine and Parasitology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Jul 24; Vol. 19 (7), pp. e0302243. Date of Electronic Publication: 2024 Jul 24 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0302243
Abstrakt: 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.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: C. F. and A. F. S. are employees of AdaptVac, a company commercializing virus-like particle display technology and vaccine, including several patents. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
(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.)
Databáze: MEDLINE
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