Protective human antibodies against Powassan virus.

Area of Science:

• Virology
• Immunology
• Neuroscience

Background:

• Powassan virus (POWV) is a tick-borne orthoflavivirus causing severe neuroinvasive disease.
• Human POWV infections are increasing, with no approved vaccines or therapeutics available.
• POWV has a significant case-fatality rate, posing a public health threat.

Purpose of the Study:

• To isolate and characterize human monoclonal antibodies (mAbs) targeting Powassan virus.
• To identify neutralizing mAbs and their epitopes on the POWV E glycoprotein.
• To evaluate the therapeutic potential of these mAbs in a preclinical model.

Main Methods:

• Single B-cell sorting was used to isolate mAbs from a convalescent donor.
• Antigen baits included POWV EDIII and full-length E ectodomain.
• Binding and neutralization assays were performed using reporter virus particles and authentic POWV strains.
• Four neutralizing mAbs were tested in a lethal mouse challenge model.

Main Results:

• Multiple neutralizing human mAbs targeting distinct epitopes on the POWV E glycoprotein were identified.
• These epitopes include regions on EDIII and other non-EDIII areas.
• Two of the four tested neutralizing mAbs provided substantial protection in mice challenged with lethal POWV.

Conclusions:

• The study defines key targets of the human antibody response to Powassan virus.
• Identified neutralizing mAbs are promising candidates for developing human monoclonal antibody therapy.
• These findings provide a foundation for future immunotherapies against POWV.