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Updated: May 10, 2026
Measuring Influenza Neutralizing Antibody Responses to A(H3N2) Viruses in Human Sera by Microneutralization Assays Using MDCK-SIAT1 Cells
Published on: November 22, 2017
Human neutralizing antibodies targeting the measles virus hemagglutinin and fusion surface proteins
Marissa Acciani1, Dawid Zyla1, Gele Niemeyer2
1Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
Abstract:
Measles virus (MeV), a highly transmissible paramyxovirus, can cause severe complications and death, particularly in infants and young children. How and where human antibodies target and neutralize MeV remain unclear. Here, we report a panel of human monoclonal antibodies (mAbs) specific for MeV hemagglutinin (H) and fusion (F) surface proteins, derived from the memory B cells of a Measles-Mumps-Rubella (MMR) vaccinee. We mapped four and five major epitope clusters on H and F, respectively, and structurally characterized representative mAbs from each epitope cluster. MAbs against both H and F offer broad, potent, picomolar-level neutralization and substantially reduce viral loads in vivo when delivered before or after viral exposure. High-resolution cryo-electron microscopy of mAb complexes with H and F reveal highly conserved contact sites of the most protective antibodies. Characterization of these fully human mAbs provides avenues for prophylactic or therapeutic intervention against re-emerging MeV.
Insights
Human monoclonal antibodies targeting measles virus (MeV) surface proteins neutralize the virus effectively. These potent antibodies, derived from MMR vaccinees, offer new therapeutic and prophylactic strategies against MeV infections.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Measles virus (MeV) is a highly contagious paramyxovirus causing severe illness, especially in young children.
- The precise mechanisms and targets of human antibody neutralization against MeV are not fully understood.
Purpose of the Study:
- To identify and characterize human monoclonal antibodies (mAbs) that neutralize MeV.
- To structurally map the epitopes targeted by these antibodies on MeV surface proteins.
Main Methods:
- Isolation of memory B cells from Measles-Mumps-Rubella (MMR) vaccinees.
- Generation and characterization of human mAbs against MeV hemagglutinin (H) and fusion (F) proteins.
- Epitope mapping and high-resolution cryo-electron microscopy (cryo-EM) studies.
Main Results:
- A panel of human mAbs targeting conserved epitopes on MeV H and F proteins was generated.
- These mAbs demonstrated broad, potent, picomolar-level neutralization of MeV.
- In vivo studies showed significant reduction in viral loads following mAb administration before or after exposure.
- Cryo-EM revealed conserved antibody binding sites crucial for neutralization.
Conclusions:
- Fully human mAbs targeting MeV H and F proteins offer promising prophylactic and therapeutic potential.
- Understanding antibody epitope targeting provides insights for developing interventions against re-emerging measles.
- These findings support the development of novel strategies to combat measles virus infections.
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