A neutralizing antibody prevents postfusion transition of measles virus fusion protein.
Science
; 384(6703): eadm8693, 2024 Jun 28.
Article
in En
| MEDLINE
| ID: mdl-38935733
ABSTRACT
Measles virus (MeV) presents a public health threat that is escalating as vaccine coverage in the general population declines and as populations of immunocompromised individuals, who cannot be vaccinated, increase. There are no approved therapeutics for MeV. Neutralizing antibodies targeting viral fusion are one potential therapeutic approach but have not yet been structurally characterized or advanced to clinical use. We present cryo-electron microscopy (cryo-EM) structures of prefusion F alone [2.1-angstrom (Å) resolution], F complexed with a fusion-inhibitory peptide (2.3-Å resolution), F complexed with the neutralizing and protective monoclonal antibody (mAb) 77 (2.6-Å resolution), and an additional structure of postfusion F (2.7-Å resolution). In vitro assays and examination of additional EM classes show that mAb 77 binds prefusion F, arrests F in an intermediate state, and prevents transition to the postfusion conformation. These structures shed light on antibody-mediated neutralization that involves arrest of fusion proteins in an intermediate state.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Viral Fusion Proteins
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Cryoelectron Microscopy
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Antibodies, Neutralizing
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Measles virus
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Antibodies, Monoclonal
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Antibodies, Viral
Limits:
Humans
Language:
En
Journal:
Science
Year:
2024
Document type:
Article