Measles Virus Hemagglutinin epitopes immunogenic in natural infection and vaccination are targeted by broad or genotype-specific neutralizing monoclonal antibodies
Copyright © 2017 Elsevier B.V. All rights reserved..
Measles virus (MV) remains a leading cause of vaccine-preventable deaths in children. Protection against MV is associated with neutralizing antibodies that preferentially recognize the viral hemagglutinin (MV-H), and to a lesser extent, the fusion protein (MV-F). Although MV is serologically monotypic, 24 genotypes have been identified. Here we report three neutralization epitopes conserved in the more prevalent circulating MV genotypes, two located in the MV-H receptor binding site (RBS) (antigenic site III) and a third in MV-H/MV-F interphase (antigenic site Ia) which are essential for MV multiplication. In contrast, two MV-H neutralization epitopes, showed a genotype-specific neutralization escape due to a single amino acid change, that we mapped in the "noose" antigenic site, or an enhanced neutralization epitope (antigenic site IIa). The monoclonal antibody (mAb) neutralization potency correlated with its binding affinity and was mainly driven by kinetic dissociation rate (koff). We developed an immunoassay for mAb binding to MV-H in its native hetero-oligomeric structure with MV-F on the surface of a MV productive steady-state persistently infected (p.i.) human cell lines, and a competitive-binding assay with serum from individuals with past infection by different MV genotypes. Binding assays revealed that a broad neutralization epitope, in RBS antigenic site, a genotype specific neutralization epitopes, in noose and IIa sites, were immunogenic in natural infection and vaccination and may elicit long-lasting humoral immunity that might contribute to explain MV immunogenic stability. These results support the design of improved measles vaccines, broad-spectrum prophylactic or therapeutic antibodies and MV-used in oncolytic therapies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:236 |
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| Enthalten in: |
Virus research - 236(2017) vom: 15. Mai, Seite 30-43 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Muñoz-Alía, Miguel Angel [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.02.2018 Date Revised 26.02.2018 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.virusres.2017.04.018 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM271508353 |
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| 100 | 1 | |a Muñoz-Alía, Miguel Angel |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Measles Virus Hemagglutinin epitopes immunogenic in natural infection and vaccination are targeted by broad or genotype-specific neutralizing monoclonal antibodies |
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| 520 | |a Copyright © 2017 Elsevier B.V. All rights reserved. | ||
| 520 | |a Measles virus (MV) remains a leading cause of vaccine-preventable deaths in children. Protection against MV is associated with neutralizing antibodies that preferentially recognize the viral hemagglutinin (MV-H), and to a lesser extent, the fusion protein (MV-F). Although MV is serologically monotypic, 24 genotypes have been identified. Here we report three neutralization epitopes conserved in the more prevalent circulating MV genotypes, two located in the MV-H receptor binding site (RBS) (antigenic site III) and a third in MV-H/MV-F interphase (antigenic site Ia) which are essential for MV multiplication. In contrast, two MV-H neutralization epitopes, showed a genotype-specific neutralization escape due to a single amino acid change, that we mapped in the "noose" antigenic site, or an enhanced neutralization epitope (antigenic site IIa). The monoclonal antibody (mAb) neutralization potency correlated with its binding affinity and was mainly driven by kinetic dissociation rate (koff). We developed an immunoassay for mAb binding to MV-H in its native hetero-oligomeric structure with MV-F on the surface of a MV productive steady-state persistently infected (p.i.) human cell lines, and a competitive-binding assay with serum from individuals with past infection by different MV genotypes. Binding assays revealed that a broad neutralization epitope, in RBS antigenic site, a genotype specific neutralization epitopes, in noose and IIa sites, were immunogenic in natural infection and vaccination and may elicit long-lasting humoral immunity that might contribute to explain MV immunogenic stability. These results support the design of improved measles vaccines, broad-spectrum prophylactic or therapeutic antibodies and MV-used in oncolytic therapies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Broad or genotype-specific neutralizing mAbs | |
| 650 | 4 | |a Hemagglutinin neutralization epitopes | |
| 650 | 4 | |a Human and macaque sera | |
| 650 | 4 | |a Immunogenicity-humoral immunity | |
| 650 | 4 | |a Measles virus primary isolates | |
| 650 | 4 | |a mAbs bindinding-kinetic rates | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 650 | 7 | |a Hemagglutinins, Viral |2 NLM | |
| 650 | 7 | |a Measles Vaccine |2 NLM | |
| 700 | 1 | |a Casasnovas, José M |e verfasserin |4 aut | |
| 700 | 1 | |a Celma, María Luisa |e verfasserin |4 aut | |
| 700 | 1 | |a Carabaña, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Liton, Paloma B |e verfasserin |4 aut | |
| 700 | 1 | |a Fernandez-Muñoz, Rafael |e verfasserin |4 aut | |
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