Neutralizing Antibodies Against Chikungunya Virus
This study reports the isolation and characterization of two neutralizing antibodies, C34 and C37, derived from a convalescent patient infected with Chikungunya virus (CHIKV).
Background on Chikungunya Virus
CHIKV is a mosquito-transmitted alphavirus responsible for febrile illness and both acute and chronic arthritis. Most current therapeutics for CHIKV remain in the preclinical development stage.
Isolation and Efficacy of Antibodies
Antibodies C34 and C37 show strong neutralizing activity in vitro and provide protective effects in a female mouse model. They target an epitope on the E2 protein, effectively blocking the Mxra8 receptor, which is essential for viral entry.
Mechanism of Action
- Both antibodies bind with high affinity to an epitope spanning the E2 and E1 proteins and their connecting β-strands.
- This binding enables both intra- and inter-virion crosslinking, interfering with multiple stages of the virus infection cycle.
- Cryo-electron microscopy (cryo-EM) identified an additional minor patch beneath the E3 binding site on E2, exposed when E3 dissociates during virus maturation.
- Binding to the CHIKV receptor Mxra8 is blocked due to steric clash between the antibodies and the stalk region of Mxra8.
"Both antibodies bind with high affinity to an epitope spanning E2, E1, and the connecting β-strands, facilitating intra- and inter-virion crosslinking."
"Functional and structural data further suggest that binding to the CHIKV receptor, Mxra8, is obstructed due to a clash between the antibodies and the stalk region of Mxra8."
Significance
The study demonstrates that C34 and C37 neutralizing antibodies interfere at multiple stages of CHIKV infection by blocking crucial viral and host interactions, offering promising therapeutic potential.
Author's summary: Antibodies C34 and C37 isolated from a recovered patient neutralize Chikungunya virus by binding key viral proteins and blocking receptor access, revealing a multifaceted antiviral mechanism.