Human-like antibodies neutralizing Western equine encephalitis virus

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Western equine encephalitis virus (WEEV) is a mosquito-borne alphavirus posing significant neurological health risks.
• WEEV is a U.S. CDC-classified biowarfare agent with no existing antiviral treatments.
• Neutralizing antibodies are critical for preventing and treating WEEV infections.

Purpose of the Study:

• To develop and characterize novel neutralizing antibodies against WEEV.
• To evaluate the potential of these antibodies for therapeutic applications and passive vaccine development.

Main Methods:

• Construction of immune antibody gene libraries from WEEV-immunized macaques.
• Selection and recloning of antibodies as scFv-Fc fusion proteins.
• Characterization of antibody binding specificity (ELISA, immunohistochemistry) and in vitro neutralizing activity.

Main Results:

• Four specific WEEV-binding antibodies were identified.
• Three antibodies demonstrated potent in vitro neutralizing activity against WEEV.
• The lead antibody, ToR69-3A2, exhibited high neutralization efficacy (EC50 ~1 ng/mL) and human-like characteristics.

Conclusions:

• The identified neutralizing antibodies are effective against WEEV and suitable for intracellular detection.
• The ToR69-3A2 antibody is a promising candidate for the development of a WEEV passive vaccine.
• This research addresses a critical unmet need for WEEV therapeutics.