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Measles Virus Hemagglutinin epitopes immunogenic in natural infection and vaccination are targeted by broad or genotype-specific neutralizing monoclonal antibodies.
- Source :
-
Virus research [Virus Res] 2017 May 15; Vol. 236, pp. 30-43. Date of Electronic Publication: 2017 Apr 29. - Publication Year :
- 2017
-
Abstract
- 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 (k <subscript>off</subscript> ). 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.<br /> (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Subjects :
- Antibodies, Neutralizing immunology
Epitopes administration & dosage
Epitopes immunology
Genotype
Hemagglutinins, Viral administration & dosage
Hemagglutinins, Viral genetics
Humans
Measles prevention & control
Measles virology
Measles Vaccine administration & dosage
Measles Vaccine immunology
Measles virus classification
Measles virus genetics
Measles virus isolation & purification
Neutralization Tests
Vaccination
Antibodies, Monoclonal immunology
Antibodies, Viral immunology
Hemagglutinins, Viral immunology
Measles immunology
Measles virus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7492
- Volume :
- 236
- Database :
- MEDLINE
- Journal :
- Virus research
- Publication Type :
- Academic Journal
- Accession number :
- 28465158
- Full Text :
- https://doi.org/10.1016/j.virusres.2017.04.018