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Characterization of an Isotype-Dependent Monoclonal Antibody against Linear Neutralizing Epitope Effective for Prophylaxis of Enterovirus 71 Infection
BACKGROUND: Enterovirus 71 (EV71) is the main causative agent of Hand, Foot and Mouth disease (HFMD) and is associated with severe neurologic complications and mortalities. At present, there is no vaccine or therapeutic available for treatment. METHODOLOGY/PRINCIPAL FINDING: In this study, we genera...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261156/ https://www.ncbi.nlm.nih.gov/pubmed/22279543 http://dx.doi.org/10.1371/journal.pone.0029751 |
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author | Lim, Xiao Fang Jia, Qiang Khong, Wei Xin Yan, Benedict Premanand, Balraj Alonso, Sylvie Chow, Vincent T. K. Kwang, Jimmy |
author_facet | Lim, Xiao Fang Jia, Qiang Khong, Wei Xin Yan, Benedict Premanand, Balraj Alonso, Sylvie Chow, Vincent T. K. Kwang, Jimmy |
author_sort | Lim, Xiao Fang |
collection | PubMed |
description | BACKGROUND: Enterovirus 71 (EV71) is the main causative agent of Hand, Foot and Mouth disease (HFMD) and is associated with severe neurologic complications and mortalities. At present, there is no vaccine or therapeutic available for treatment. METHODOLOGY/PRINCIPAL FINDING: In this study, we generated two mAbs, denoted as mAb 51 and 53, both targeting the same linear epitope on VP1 capsid protein, spanning amino acids 215–219. In comparison, mAb 51 belonging to isotype IgM possesses neutralizing activity in vitro, whereas, mAb 53 belonging to isotype IgG1 does not have any neutralizing ability, even towards its homologous strain. When mAb 51 at 10 µg/g of body weight was administered to the 2-week-old AG129 mice one day prior to lethal challenge, 100% in vivo passive protection was observed. In contrast, the isotype control group mice, injected with an irrelevant IgM antibody before the challenge, developed limb paralysis as early as day 6 post-infection. Histological examination demonstrated that mAb 51 was able to protect against pathologic changes such as neuropil vacuolation and neuronal loss in the spinal cord, which were typical in unprotected EV-71 infected mice. BLAST analyses of that epitope revealed that it was highly conserved among all EV71 strains, but not coxsachievirus 16 (CA16). CONCLUSION: We have defined a linear epitope within the VP1 protein and demonstrated its neutralizing ability to be isotype dependent. The neutralizing property and highly conserved sequence potentiated the application of mAb 51 and 53 for protection against EV71 infection and diagnosis respectively. |
format | Online Article Text |
id | pubmed-3261156 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32611562012-01-25 Characterization of an Isotype-Dependent Monoclonal Antibody against Linear Neutralizing Epitope Effective for Prophylaxis of Enterovirus 71 Infection Lim, Xiao Fang Jia, Qiang Khong, Wei Xin Yan, Benedict Premanand, Balraj Alonso, Sylvie Chow, Vincent T. K. Kwang, Jimmy PLoS One Research Article BACKGROUND: Enterovirus 71 (EV71) is the main causative agent of Hand, Foot and Mouth disease (HFMD) and is associated with severe neurologic complications and mortalities. At present, there is no vaccine or therapeutic available for treatment. METHODOLOGY/PRINCIPAL FINDING: In this study, we generated two mAbs, denoted as mAb 51 and 53, both targeting the same linear epitope on VP1 capsid protein, spanning amino acids 215–219. In comparison, mAb 51 belonging to isotype IgM possesses neutralizing activity in vitro, whereas, mAb 53 belonging to isotype IgG1 does not have any neutralizing ability, even towards its homologous strain. When mAb 51 at 10 µg/g of body weight was administered to the 2-week-old AG129 mice one day prior to lethal challenge, 100% in vivo passive protection was observed. In contrast, the isotype control group mice, injected with an irrelevant IgM antibody before the challenge, developed limb paralysis as early as day 6 post-infection. Histological examination demonstrated that mAb 51 was able to protect against pathologic changes such as neuropil vacuolation and neuronal loss in the spinal cord, which were typical in unprotected EV-71 infected mice. BLAST analyses of that epitope revealed that it was highly conserved among all EV71 strains, but not coxsachievirus 16 (CA16). CONCLUSION: We have defined a linear epitope within the VP1 protein and demonstrated its neutralizing ability to be isotype dependent. The neutralizing property and highly conserved sequence potentiated the application of mAb 51 and 53 for protection against EV71 infection and diagnosis respectively. Public Library of Science 2012-01-18 /pmc/articles/PMC3261156/ /pubmed/22279543 http://dx.doi.org/10.1371/journal.pone.0029751 Text en Lim et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Lim, Xiao Fang Jia, Qiang Khong, Wei Xin Yan, Benedict Premanand, Balraj Alonso, Sylvie Chow, Vincent T. K. Kwang, Jimmy Characterization of an Isotype-Dependent Monoclonal Antibody against Linear Neutralizing Epitope Effective for Prophylaxis of Enterovirus 71 Infection |
title | Characterization of an Isotype-Dependent Monoclonal Antibody against Linear Neutralizing Epitope Effective for Prophylaxis of Enterovirus 71 Infection |
title_full | Characterization of an Isotype-Dependent Monoclonal Antibody against Linear Neutralizing Epitope Effective for Prophylaxis of Enterovirus 71 Infection |
title_fullStr | Characterization of an Isotype-Dependent Monoclonal Antibody against Linear Neutralizing Epitope Effective for Prophylaxis of Enterovirus 71 Infection |
title_full_unstemmed | Characterization of an Isotype-Dependent Monoclonal Antibody against Linear Neutralizing Epitope Effective for Prophylaxis of Enterovirus 71 Infection |
title_short | Characterization of an Isotype-Dependent Monoclonal Antibody against Linear Neutralizing Epitope Effective for Prophylaxis of Enterovirus 71 Infection |
title_sort | characterization of an isotype-dependent monoclonal antibody against linear neutralizing epitope effective for prophylaxis of enterovirus 71 infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261156/ https://www.ncbi.nlm.nih.gov/pubmed/22279543 http://dx.doi.org/10.1371/journal.pone.0029751 |
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