Neutralizing antibodies against Chikungunya virus and structural elucidation of their mechanism of action

Neutralizing Antibodies Against Chikungunya Virus

This study reports the isolation and characterization of two neutralizing antibodies, C34 and C37, derived from a convalescent patient who recovered from Chikungunya virus (CHIKV) infection.

Antibody Efficacy and Target

C34 and C37 show strong neutralizing activity against CHIKV both in vitro and in vivo.
They target a specific epitope on the viral E2 protein.
The antibodies effectively block the Mxra8 receptor, which is crucial for virus entry.

Background on Chikungunya Virus

CHIKV is a mosquito-transmitted alphavirus that causes febrile illness and can lead to acute or chronic arthritis. Currently, most treatments for CHIKV remain in preclinical development.

Mechanism of Action

The antibodies interfere with multiple stages of CHIKV's infection cycle by binding with high affinity to an epitope spanning the E2, E1 proteins, and connecting β-strands. This binding promotes crosslinking between and within virions.

Cryo-electron microscopy (Cryo-EM) revealed a minor binding patch beneath the E3 site on E2 that becomes exposed after E3 dissociates during virus maturation.

Functional and structural evidence indicates that antibody binding obstructs CHIKV's receptor, Mxra8, due to a clash with Mxra8's stalk region.

Protective Effects in Animal Models

Both C34 and C37 provided protection in female mouse models challenged with CHIKV, confirming their therapeutic potential.

Significance

This research sheds light on a multi-step viral inhibition mechanism by antibodies, highlighting their potential use in therapy against CHIKV infections.

Author’s summary: Two neutralizing antibodies from a recovered patient block Chikungunya virus infection by targeting key viral proteins and obstructing receptor binding, offering a promising therapeutic approach.

Nature — 2025-11-04