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Measles Virus Hemagglutinin epitopes immunogenic in natural infection and vaccination are targeted by broad or genotype-specific neutralizing monoclonal antibodies.
Virus Res. 2017 05 15; 236:30-43.VR

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 (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.

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Authors+Show Affiliations

Muñoz-Alía MA
Virology Unit, Ramón y Cajal Hospital, Madrid, Spain.
Casasnovas JM
Centro Nacional de Biotecnología, Cantoblanco, 28049 Madrid, Spain.
Celma ML
Virology Unit, Ramón y Cajal Hospital, Madrid, Spain.
Carabaña J
Virology Unit, Ramón y Cajal Hospital, Madrid, Spain.
Liton PB
Virology Unit, Ramón y Cajal Hospital, Madrid, Spain.
Fernandez-Muñoz R
Virology Unit, Ramón y Cajal Hospital, Madrid, Spain. Electronic address: rafael.fernandez.mu@gmail.com.

MeSH

Antibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralEpitopesGenotypeHemagglutinins, ViralHumansMeaslesMeasles VaccineMeasles virusNeutralization TestsVaccination

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28465158

Citation

Muñoz-Alía, Miguel Angel, et al. "Measles Virus Hemagglutinin Epitopes Immunogenic in Natural Infection and Vaccination Are Targeted By Broad or Genotype-specific Neutralizing Monoclonal Antibodies." Virus Research, vol. 236, 2017, pp. 30-43.
Muñoz-Alía MA, Casasnovas JM, Celma ML, et al. Measles Virus Hemagglutinin epitopes immunogenic in natural infection and vaccination are targeted by broad or genotype-specific neutralizing monoclonal antibodies. Virus Res. 2017;236:30-43.
Muñoz-Alía, M. A., Casasnovas, J. M., Celma, M. L., Carabaña, J., Liton, P. B., & Fernandez-Muñoz, R. (2017). Measles Virus Hemagglutinin epitopes immunogenic in natural infection and vaccination are targeted by broad or genotype-specific neutralizing monoclonal antibodies. Virus Research, 236, 30-43. https://doi.org/10.1016/j.virusres.2017.04.018
Muñoz-Alía MA, et al. Measles Virus Hemagglutinin Epitopes Immunogenic in Natural Infection and Vaccination Are Targeted By Broad or Genotype-specific Neutralizing Monoclonal Antibodies. Virus Res. 2017 05 15;236:30-43. PubMed PMID: 28465158.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Measles Virus Hemagglutinin epitopes immunogenic in natural infection and vaccination are targeted by broad or genotype-specific neutralizing monoclonal antibodies. AU - Muñoz-Alía,Miguel Angel, AU - Casasnovas,José M, AU - Celma,María Luisa, AU - Carabaña,Juan, AU - Liton,Paloma B, AU - Fernandez-Muñoz,Rafael, Y1 - 2017/04/29/ PY - 2017/02/06/received PY - 2017/04/24/revised PY - 2017/04/24/accepted PY - 2017/5/4/pubmed PY - 2018/2/10/medline PY - 2017/5/4/entrez KW - Broad or genotype-specific neutralizing mAbs KW - Hemagglutinin neutralization epitopes KW - Human and macaque sera KW - Immunogenicity-humoral immunity KW - Measles virus primary isolates KW - mAbs bindinding-kinetic rates SP - 30 EP - 43 JF - Virus research JO - Virus Res VL - 236 N2 - 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. SN - 1872-7492 UR - https://www.unboundmedicine.com/medline/citation/28465158/Measles_Virus_Hemagglutinin_epitopes_immunogenic_in_natural_infection_and_vaccination_are_targeted_by_broad_or_genotype_specific_neutralizing_monoclonal_antibodies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-1702(17)30127-2 DB - PRIME DP - Unbound Medicine ER -