A novel universal neutralizing monoclonal antibody against enterovirus 71 that targets the highly conserved "knob" region of VP3 protein.
Hand, foot and mouth disease caused by enterovirus 71(EV71) leads to the majority of neurological complications and death in young children. While putative inactivated vaccines are only now undergoing clinical trials, no specific treatment options exist yet. Ideally, EV71 specific intravenous immuno...
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ftdoajarticles:oai:doaj.org/article:aaa8503ba34c4c82b5a3af5fb8bf5d12 2023-05-15T15:09:19+02:00 A novel universal neutralizing monoclonal antibody against enterovirus 71 that targets the highly conserved "knob" region of VP3 protein. Tanja K Kiener Qiang Jia Tao Meng Vincent Tak Kwong Chow Jimmy Kwang 2014-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002895 https://doaj.org/article/aaa8503ba34c4c82b5a3af5fb8bf5d12 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4038473?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002895 https://doaj.org/article/aaa8503ba34c4c82b5a3af5fb8bf5d12 PLoS Neglected Tropical Diseases, Vol 8, Iss 5, p e2895 (2014) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2014 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002895 2022-12-31T01:32:52Z Hand, foot and mouth disease caused by enterovirus 71(EV71) leads to the majority of neurological complications and death in young children. While putative inactivated vaccines are only now undergoing clinical trials, no specific treatment options exist yet. Ideally, EV71 specific intravenous immunoglobulins could be developed for targeted treatment of severe cases. To date, only a single universally neutralizing monoclonal antibody against a conserved linear epitope of VP1 has been identified. Other enteroviruses have been shown to possess major conformational neutralizing epitopes on both the VP2 and VP3 capsid proteins. Hence, we attempted to isolate such neutralizing antibodies against conformational epitopes for their potential in the treatment of infection as well as differential diagnosis and vaccine optimization. Here we describe a universal neutralizing monoclonal antibody that recognizes a conserved conformational epitope of EV71 which was mapped using escape mutants. Eight escape mutants from different subgenogroups (A, B2, B4, C2, C4) were rescued; they harbored three essential mutations either at amino acid positions 59, 62 or 67 of the VP3 protein which are all situated in the "knob" region. The escape mutant phenotype could be mimicked by incorporating these mutations into reverse genetically engineered viruses showing that P59L, A62D, A62P and E67D abolish both monoclonal antibody binding and neutralization activity. This is the first conformational neutralization epitope mapped on VP3 for EV71. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic The Knob ENVELOPE(-131.721,-131.721,56.850,56.850) PLoS Neglected Tropical Diseases 8 5 e2895 |
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 Tanja K Kiener Qiang Jia Tao Meng Vincent Tak Kwong Chow Jimmy Kwang A novel universal neutralizing monoclonal antibody against enterovirus 71 that targets the highly conserved "knob" region of VP3 protein. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Hand, foot and mouth disease caused by enterovirus 71(EV71) leads to the majority of neurological complications and death in young children. While putative inactivated vaccines are only now undergoing clinical trials, no specific treatment options exist yet. Ideally, EV71 specific intravenous immunoglobulins could be developed for targeted treatment of severe cases. To date, only a single universally neutralizing monoclonal antibody against a conserved linear epitope of VP1 has been identified. Other enteroviruses have been shown to possess major conformational neutralizing epitopes on both the VP2 and VP3 capsid proteins. Hence, we attempted to isolate such neutralizing antibodies against conformational epitopes for their potential in the treatment of infection as well as differential diagnosis and vaccine optimization. Here we describe a universal neutralizing monoclonal antibody that recognizes a conserved conformational epitope of EV71 which was mapped using escape mutants. Eight escape mutants from different subgenogroups (A, B2, B4, C2, C4) were rescued; they harbored three essential mutations either at amino acid positions 59, 62 or 67 of the VP3 protein which are all situated in the "knob" region. The escape mutant phenotype could be mimicked by incorporating these mutations into reverse genetically engineered viruses showing that P59L, A62D, A62P and E67D abolish both monoclonal antibody binding and neutralization activity. This is the first conformational neutralization epitope mapped on VP3 for EV71. |
format |
Article in Journal/Newspaper |
author |
Tanja K Kiener Qiang Jia Tao Meng Vincent Tak Kwong Chow Jimmy Kwang |
author_facet |
Tanja K Kiener Qiang Jia Tao Meng Vincent Tak Kwong Chow Jimmy Kwang |
author_sort |
Tanja K Kiener |
title |
A novel universal neutralizing monoclonal antibody against enterovirus 71 that targets the highly conserved "knob" region of VP3 protein. |
title_short |
A novel universal neutralizing monoclonal antibody against enterovirus 71 that targets the highly conserved "knob" region of VP3 protein. |
title_full |
A novel universal neutralizing monoclonal antibody against enterovirus 71 that targets the highly conserved "knob" region of VP3 protein. |
title_fullStr |
A novel universal neutralizing monoclonal antibody against enterovirus 71 that targets the highly conserved "knob" region of VP3 protein. |
title_full_unstemmed |
A novel universal neutralizing monoclonal antibody against enterovirus 71 that targets the highly conserved "knob" region of VP3 protein. |
title_sort |
novel universal neutralizing monoclonal antibody against enterovirus 71 that targets the highly conserved "knob" region of vp3 protein. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doi.org/10.1371/journal.pntd.0002895 https://doaj.org/article/aaa8503ba34c4c82b5a3af5fb8bf5d12 |
long_lat |
ENVELOPE(-131.721,-131.721,56.850,56.850) |
geographic |
Arctic The Knob |
geographic_facet |
Arctic The Knob |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 8, Iss 5, p e2895 (2014) |
op_relation |
http://europepmc.org/articles/PMC4038473?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002895 https://doaj.org/article/aaa8503ba34c4c82b5a3af5fb8bf5d12 |
op_doi |
https://doi.org/10.1371/journal.pntd.0002895 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
8 |
container_issue |
5 |
container_start_page |
e2895 |
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1766340538480459776 |