Human mAbs Broadly Protect against Arthritogenic Alphaviruses by Recognizing Conserved Elements of the Mxra8...

Area of Science:

• Virology
• Immunology
• Structural Biology

Background:

• Arthritogenic alphaviruses cause significant global health burdens, including fever, severe musculoskeletal pain, and arthritis.
• Current therapeutic and vaccine options for these infections are limited, necessitating novel treatment strategies.

Purpose of the Study:

• To identify and characterize broadly neutralizing human monoclonal antibodies (mAbs) against arthritogenic alphaviruses.
• To elucidate the mechanism of neutralization and identify potential therapeutic targets.

Main Methods:

• Generation and characterization of human monoclonal antibodies (mAbs).
• Cryoelectron microscopy to determine structures of mAbs complexed with alphaviruses.
• In vitro neutralization assays and in vivo protection studies in mouse models.

Main Results:

• Identified human mAbs that bind and neutralize multiple alphaviruses, including Ross River, Mayaro, and chikungunya viruses.
• Structural analysis revealed a conserved epitope on the E2 glycoprotein targeted by a broadly neutralizing mAb (RRV-12).
• The RRV-12 mAb demonstrated in vitro neutralization by blocking viral attachment to the Mxra8 receptor and in vivo protection in mouse models.

Conclusions:

• The identified broadly neutralizing mAb RRV-12 offers a promising therapeutic candidate against diverse alphavirus infections.
• The conserved epitope represents a potential target for the development of novel vaccines against emerging alphavirus diseases.