Protective threshold of a potent neutralizing Zika virus monoclonal antibody in rhesus macaques

Area of Science:

• Virology
• Immunology
• Pharmacology

Background:

• Zika virus (ZIKV) poses a continued global health threat, with no approved vaccine available.
• Neutralizing monoclonal antibodies (mAbs) are a promising alternative for ZIKV prevention and treatment.
• Previous research identified ZIKV-117 mAb, showing efficacy in protecting mice against ZIKV infection.

Purpose of the Study:

• To evaluate the protective efficacy of an engineered human mAb, ZIKV-117-LALA-YTE, against ZIKV challenge in a non-human primate model.
• To determine the potency and effective dosage of ZIKV-117-LALA-YTE in rhesus macaques.

Main Methods:

• A titration study was conducted in rhesus macaques challenged with ZIKV.
• The engineered mAb, ZIKV-117-LALA-YTE, was administered at varying doses.
• Serum concentrations of the mAb and protection against ZIKV infection were assessed.

Main Results:

• Complete protection against ZIKV challenge was achieved at a remarkably low dose of 0.016 mg/kg.
• The median serum concentration of ZIKV-117-LALA-YTE at this protective dose was 0.13 µg/mL.
• The engineered mAb exhibited exquisite potency in protecting macaques.

Conclusions:

• ZIKV-117-LALA-YTE demonstrates high potency and efficacy in a relevant animal model.
• The engineered mAb warrants further clinical development as a potential biotherapeutic for ZIKV.
• This study supports the use of ZIKV-specific neutralizing antibodies for ZIKV infection control.