Human monoclonal anti-HCMV neutralizing antibody from phage display libraries

Area of Science:

• Virology
• Immunology
• Biotechnology

Background:

• Human cytomegalovirus (HCMV) infection poses significant risks to immunocompromised individuals.
• Current ganciclovir prophylaxis for HCMV has limitations due to severe side effects.
• Novel prophylactic strategies are crucial for managing HCMV infections.

Purpose of the Study:

• To clone a recombinant human Fab fragment targeting HCMV using phage display.
• To evaluate the efficacy and specificity of the developed antibody fragment against HCMV.

Main Methods:

• Construction and panning of a 4 x 10^6 clone phage display library against HCMV-infected cell lysates.
• Screening of antigen-binding clones using ELISA.
• Immunostaining of HCMV-infected cells at various time points post-infection.
• Assessment of neutralizing activity against HCMV plaque formation and other herpesviruses.

Main Results:

• One human Fab fragment showed strong reactivity to HCMV.
• The antibody stained HCMV-infected cells from 24 to 96 hours post-infection, indicating late-phase protein synthesis.
• The Fab fragment demonstrated neutralizing activity, reducing HCMV plaque formation by 50% at 1 µg/ml.
• The antibody neutralized three HCMV strains but not HSV-1 or HSV-2.

Conclusions:

• A novel human Fab fragment targeting HCMV has been successfully cloned and characterized.
• This antibody recognizes a late-phase HCMV protein and possesses significant neutralizing activity.
• The developed human monoclonal antibody fragment represents a promising candidate for future HCMV prophylaxis strategies.