Design, expression, and characterization of a multivalent, combination HIV microbicide

Area of Science:

• Biotechnology
• Immunology
• Virology

Background:

• Protein-based microbicides, including monoclonal antibodies (mAbs), show promise for HIV prevention.
• Developing effective microbicides often requires combining multiple agents for broad and lasting protection.
• Plant-based production offers potential for scalable and cost-effective manufacturing of biologics.

Purpose of the Study:

• To express and characterize a fusion protein combining the HIV-neutralizing monoclonal antibody b12 with cyanovirin-N (CV-N) in transgenic plants.
• To evaluate the functionality, binding activity, and anti-HIV potency of the plant-derived fusion protein.
• To assess the potential of this plant-produced fusion protein as a combinational microbicide strategy.

Main Methods:

• Expression of a fusion protein comprising mAb b12 and CV-N in transgenic plants (in planta).
• In vitro assessment of gp120 binding activity for both individual moieties and the fusion protein.
• In vitro evaluation of HIV neutralization capacity of the fusion protein compared to individual components.

Main Results:

• The plant-derived fusion protein demonstrated functional gp120 binding activity.
• Both mAb b12 and CV-N moieties retained their binding capabilities within the fusion protein.
• The fusion protein exhibited enhanced in vitro HIV neutralization potency compared to b12 or CV-N alone.
• Successful assembly and expression of the functional fusion protein in planta were achieved.

Conclusions:

• A fusion protein combining mAb b12 and CV-N can be successfully produced in plants.
• This plant-produced fusion protein retains the functional binding and neutralization activities of its components.
• The fusion protein demonstrates increased potency and addresses the need for combinational microbicides, with plant production offering a scalable manufacturing approach for global accessibility.