A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions.
BACKGROUND:A vaccine targeting Plasmodium vivax will be an essential component of any comprehensive malaria elimination program, but major gaps in our understanding of P. vivax biology, including the protein-protein interactions that mediate merozoite invasion of reticulocytes, hinder the search for...
Published in: | PLOS Neglected Tropical Diseases |
---|---|
Main Authors: | , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2015
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0004264 https://doaj.org/article/0fbe5be016614fdeaf7f0fe3e15c42e8 |
id |
ftdoajarticles:oai:doaj.org/article:0fbe5be016614fdeaf7f0fe3e15c42e8 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:0fbe5be016614fdeaf7f0fe3e15c42e8 2023-05-15T15:15:16+02:00 A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions. Jessica B Hostetler Sumana Sharma S Josefin Bartholdson Gavin J Wright Rick M Fairhurst Julian C Rayner 2015-12-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0004264 https://doaj.org/article/0fbe5be016614fdeaf7f0fe3e15c42e8 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4689532?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004264 https://doaj.org/article/0fbe5be016614fdeaf7f0fe3e15c42e8 PLoS Neglected Tropical Diseases, Vol 9, Iss 12, p e0004264 (2015) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2015 ftdoajarticles https://doi.org/10.1371/journal.pntd.0004264 2022-12-31T01:36:33Z BACKGROUND:A vaccine targeting Plasmodium vivax will be an essential component of any comprehensive malaria elimination program, but major gaps in our understanding of P. vivax biology, including the protein-protein interactions that mediate merozoite invasion of reticulocytes, hinder the search for candidate antigens. Only one ligand-receptor interaction has been identified, that between P. vivax Duffy Binding Protein (PvDBP) and the erythrocyte Duffy Antigen Receptor for Chemokines (DARC), and strain-specific immune responses to PvDBP make it a complex vaccine target. To broaden the repertoire of potential P. vivax merozoite-stage vaccine targets, we exploited a recent breakthrough in expressing full-length ectodomains of Plasmodium proteins in a functionally-active form in mammalian cells and initiated a large-scale study of P. vivax merozoite proteins that are potentially involved in reticulocyte binding and invasion. METHODOLOGY/PRINCIPAL FINDINGS:We selected 39 P. vivax proteins that are predicted to localize to the merozoite surface or invasive secretory organelles, some of which show homology to P. falciparum vaccine candidates. Of these, we were able to express 37 full-length protein ectodomains in a mammalian expression system, which has been previously used to express P. falciparum invasion ligands such as PfRH5. To establish whether the expressed proteins were correctly folded, we assessed whether they were recognized by antibodies from Cambodian patients with acute vivax malaria. IgG from these samples showed at least a two-fold change in reactivity over naïve controls in 27 of 34 antigens tested, and the majority showed heat-labile IgG immunoreactivity, suggesting the presence of conformation-sensitive epitopes and native tertiary protein structures. Using a method specifically designed to detect low-affinity, extracellular protein-protein interactions, we confirmed a predicted interaction between P. vivax 6-cysteine proteins P12 and P41, further suggesting that the proteins are natively folded and ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 9 12 e0004264 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Jessica B Hostetler Sumana Sharma S Josefin Bartholdson Gavin J Wright Rick M Fairhurst Julian C Rayner A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:A vaccine targeting Plasmodium vivax will be an essential component of any comprehensive malaria elimination program, but major gaps in our understanding of P. vivax biology, including the protein-protein interactions that mediate merozoite invasion of reticulocytes, hinder the search for candidate antigens. Only one ligand-receptor interaction has been identified, that between P. vivax Duffy Binding Protein (PvDBP) and the erythrocyte Duffy Antigen Receptor for Chemokines (DARC), and strain-specific immune responses to PvDBP make it a complex vaccine target. To broaden the repertoire of potential P. vivax merozoite-stage vaccine targets, we exploited a recent breakthrough in expressing full-length ectodomains of Plasmodium proteins in a functionally-active form in mammalian cells and initiated a large-scale study of P. vivax merozoite proteins that are potentially involved in reticulocyte binding and invasion. METHODOLOGY/PRINCIPAL FINDINGS:We selected 39 P. vivax proteins that are predicted to localize to the merozoite surface or invasive secretory organelles, some of which show homology to P. falciparum vaccine candidates. Of these, we were able to express 37 full-length protein ectodomains in a mammalian expression system, which has been previously used to express P. falciparum invasion ligands such as PfRH5. To establish whether the expressed proteins were correctly folded, we assessed whether they were recognized by antibodies from Cambodian patients with acute vivax malaria. IgG from these samples showed at least a two-fold change in reactivity over naïve controls in 27 of 34 antigens tested, and the majority showed heat-labile IgG immunoreactivity, suggesting the presence of conformation-sensitive epitopes and native tertiary protein structures. Using a method specifically designed to detect low-affinity, extracellular protein-protein interactions, we confirmed a predicted interaction between P. vivax 6-cysteine proteins P12 and P41, further suggesting that the proteins are natively folded and ... |
format |
Article in Journal/Newspaper |
author |
Jessica B Hostetler Sumana Sharma S Josefin Bartholdson Gavin J Wright Rick M Fairhurst Julian C Rayner |
author_facet |
Jessica B Hostetler Sumana Sharma S Josefin Bartholdson Gavin J Wright Rick M Fairhurst Julian C Rayner |
author_sort |
Jessica B Hostetler |
title |
A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions. |
title_short |
A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions. |
title_full |
A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions. |
title_fullStr |
A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions. |
title_full_unstemmed |
A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions. |
title_sort |
library of plasmodium vivax recombinant merozoite proteins reveals new vaccine candidates and protein-protein interactions. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2015 |
url |
https://doi.org/10.1371/journal.pntd.0004264 https://doaj.org/article/0fbe5be016614fdeaf7f0fe3e15c42e8 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 9, Iss 12, p e0004264 (2015) |
op_relation |
http://europepmc.org/articles/PMC4689532?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004264 https://doaj.org/article/0fbe5be016614fdeaf7f0fe3e15c42e8 |
op_doi |
https://doi.org/10.1371/journal.pntd.0004264 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
9 |
container_issue |
12 |
container_start_page |
e0004264 |
_version_ |
1766345628024045568 |