Isolation and Characterization of Cross-Neutralizing Human Anti-V3 Single-Chain Variable Fragments (scFvs) Against...

Area of Science:

• Immunology
• Virology
• Biotechnology

Background:

• Human phase I trials indicate protective effects of anti-HIV-1 broadly neutralizing antibodies (bnAbs).
• The V3 region of the HIV-1 envelope is a conserved, immunogenic co-receptor binding site crucial for viral entry.
• Single-chain variable fragments (scFvs) are valuable for constructing targeted antibody therapies.

Purpose of the Study:

• To identify and characterize cross-reactive anti-V3 single-chain variable fragments (scFvs).
• To evaluate the neutralizing activity of identified scFvs against diverse HIV-1 subtypes.
• To provide insights for future immunogen design using molecular modeling.

Main Methods:

• Construction of a V3-specific human scFv phage recombinant library from HIV-1 infected donor PBMCs.
• Biopanning the library with subtype B (V3B) and subtype C (V3C) peptides.
• Molecular modeling to predict interactions between scFvs and V3 peptides.

Main Results:

• Identification of unique monoclonal anti-V3 scFvs with cross-reactivity to V3B and V3C peptides.
• Demonstrated cross-neutralizing activity of these scFvs against HIV-1 subtypes A, B, and C.
• Molecular modeling provided insights into scFv-peptide interaction sites.

Conclusions:

• The identified cross-reactive anti-V3 scFvs hold promise as immunotherapeutic reagents.
• These scFvs can be developed further for HIV-1 prevention and treatment strategies.
• Insights from molecular modeling can guide the design of novel immunogens.