Immunization with virus-like particles conjugated to CIDRα1 domain of Plasmodium falciparum erythrocyte membrane protein 1 induces inhibitory antibodies
Abstract Background During the erythrocytic cycle, Plasmodium falciparum malaria parasites express P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) that anchor the infected erythrocytes (IE) to the vascular lining of the host. The CIDRα1 domain of PfEMP1 is responsible for binding host endothel...
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ftdoajarticles:oai:doaj.org/article:29291b751fdf4d95952d96779e8f2e36 2023-05-15T15:15:08+02:00 Immunization with virus-like particles conjugated to CIDRα1 domain of Plasmodium falciparum erythrocyte membrane protein 1 induces inhibitory antibodies Charlotte Harmsen Louise Turner Susan Thrane Adam F. Sander Thor G. Theander Thomas Lavstsen 2020-03-01T00:00:00Z https://doi.org/10.1186/s12936-020-03201-z https://doaj.org/article/29291b751fdf4d95952d96779e8f2e36 EN eng BMC http://link.springer.com/article/10.1186/s12936-020-03201-z https://doaj.org/toc/1475-2875 doi:10.1186/s12936-020-03201-z 1475-2875 https://doaj.org/article/29291b751fdf4d95952d96779e8f2e36 Malaria Journal, Vol 19, Iss 1, Pp 1-11 (2020) Malaria Plasmodium falciparum Vaccine Virus-like particle Antigenic diversity PfEMP1 Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2020 ftdoajarticles https://doi.org/10.1186/s12936-020-03201-z 2022-12-30T23:30:05Z Abstract Background During the erythrocytic cycle, Plasmodium falciparum malaria parasites express P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) that anchor the infected erythrocytes (IE) to the vascular lining of the host. The CIDRα1 domain of PfEMP1 is responsible for binding host endothelial protein C receptor (EPCR), and increasing evidence support that this interaction triggers severe malaria, accounting for the majority of malaria-related deaths. In high transmission regions, children develop immunity to severe malaria after the first few infections. This immunity is believed to be mediated by antibodies targeting and inhibiting PfEMP1, causing infected erythrocytes to circulate and be cleared in the spleen. The development of immunity to malaria coincides with acquisition of broad antibody reactivity across the CIDRα1 protein family. Altogether, this identifies CIDRα1 as an important vaccine target. However, the antigenic diversity of the CIDRα1 domain family is a challenge for vaccine development. Methods Immune responses in mice vaccinated with Virus-Like Particles (VLP) presenting CIDRα1 antigens were investigated. Antibody reactivity was tested to a panel of recombinant CIDRα1 domains, and the antibodies ability to inhibit EPCR binding by the recombinant CIDRα1 domains was tested in Luminex-based multiplex assays. Results VLP-presented CIDRα1.4 antigens induced a rapid and strong IgG response capable of inhibiting EPCR-binding of multiple CIDRα1 domains mainly within the group A CIDRα1.4–7 subgroups. Conclusions The study observations mirror those from previous CIDRα1 vaccine studies using other vaccine constructs and platforms. This suggests that broad CIDRα1 antibody reactivity may be achieved through vaccination with a limited number of CIDRα1 variants. In addition, this study suggest that this may be achieved through vaccination with a human compatible VLP vaccine platform. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 19 1 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
topic |
Malaria Plasmodium falciparum Vaccine Virus-like particle Antigenic diversity PfEMP1 Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Malaria Plasmodium falciparum Vaccine Virus-like particle Antigenic diversity PfEMP1 Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Charlotte Harmsen Louise Turner Susan Thrane Adam F. Sander Thor G. Theander Thomas Lavstsen Immunization with virus-like particles conjugated to CIDRα1 domain of Plasmodium falciparum erythrocyte membrane protein 1 induces inhibitory antibodies |
topic_facet |
Malaria Plasmodium falciparum Vaccine Virus-like particle Antigenic diversity PfEMP1 Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background During the erythrocytic cycle, Plasmodium falciparum malaria parasites express P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) that anchor the infected erythrocytes (IE) to the vascular lining of the host. The CIDRα1 domain of PfEMP1 is responsible for binding host endothelial protein C receptor (EPCR), and increasing evidence support that this interaction triggers severe malaria, accounting for the majority of malaria-related deaths. In high transmission regions, children develop immunity to severe malaria after the first few infections. This immunity is believed to be mediated by antibodies targeting and inhibiting PfEMP1, causing infected erythrocytes to circulate and be cleared in the spleen. The development of immunity to malaria coincides with acquisition of broad antibody reactivity across the CIDRα1 protein family. Altogether, this identifies CIDRα1 as an important vaccine target. However, the antigenic diversity of the CIDRα1 domain family is a challenge for vaccine development. Methods Immune responses in mice vaccinated with Virus-Like Particles (VLP) presenting CIDRα1 antigens were investigated. Antibody reactivity was tested to a panel of recombinant CIDRα1 domains, and the antibodies ability to inhibit EPCR binding by the recombinant CIDRα1 domains was tested in Luminex-based multiplex assays. Results VLP-presented CIDRα1.4 antigens induced a rapid and strong IgG response capable of inhibiting EPCR-binding of multiple CIDRα1 domains mainly within the group A CIDRα1.4–7 subgroups. Conclusions The study observations mirror those from previous CIDRα1 vaccine studies using other vaccine constructs and platforms. This suggests that broad CIDRα1 antibody reactivity may be achieved through vaccination with a limited number of CIDRα1 variants. In addition, this study suggest that this may be achieved through vaccination with a human compatible VLP vaccine platform. |
format |
Article in Journal/Newspaper |
author |
Charlotte Harmsen Louise Turner Susan Thrane Adam F. Sander Thor G. Theander Thomas Lavstsen |
author_facet |
Charlotte Harmsen Louise Turner Susan Thrane Adam F. Sander Thor G. Theander Thomas Lavstsen |
author_sort |
Charlotte Harmsen |
title |
Immunization with virus-like particles conjugated to CIDRα1 domain of Plasmodium falciparum erythrocyte membrane protein 1 induces inhibitory antibodies |
title_short |
Immunization with virus-like particles conjugated to CIDRα1 domain of Plasmodium falciparum erythrocyte membrane protein 1 induces inhibitory antibodies |
title_full |
Immunization with virus-like particles conjugated to CIDRα1 domain of Plasmodium falciparum erythrocyte membrane protein 1 induces inhibitory antibodies |
title_fullStr |
Immunization with virus-like particles conjugated to CIDRα1 domain of Plasmodium falciparum erythrocyte membrane protein 1 induces inhibitory antibodies |
title_full_unstemmed |
Immunization with virus-like particles conjugated to CIDRα1 domain of Plasmodium falciparum erythrocyte membrane protein 1 induces inhibitory antibodies |
title_sort |
immunization with virus-like particles conjugated to cidrα1 domain of plasmodium falciparum erythrocyte membrane protein 1 induces inhibitory antibodies |
publisher |
BMC |
publishDate |
2020 |
url |
https://doi.org/10.1186/s12936-020-03201-z https://doaj.org/article/29291b751fdf4d95952d96779e8f2e36 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 19, Iss 1, Pp 1-11 (2020) |
op_relation |
http://link.springer.com/article/10.1186/s12936-020-03201-z https://doaj.org/toc/1475-2875 doi:10.1186/s12936-020-03201-z 1475-2875 https://doaj.org/article/29291b751fdf4d95952d96779e8f2e36 |
op_doi |
https://doi.org/10.1186/s12936-020-03201-z |
container_title |
Malaria Journal |
container_volume |
19 |
container_issue |
1 |
_version_ |
1766345520298590208 |