CD4-Binding Site Directed Cross-Neutralizing scFv Monoclonals from HIV-1 Subtype C Infected Indian Children.

Area of Science:

• Immunology
• Virology
• Biotechnology

Background:

• Human immunodeficiency virus type-1 (HIV-1) infection progresses faster in children than adults.
• HIV-1 subtype C is the predominant global strain, especially in India.
• Current HIV-1 vaccines are ineffective, necessitating alternative therapeutic strategies like broadly neutralizing antibodies (bnAbs).

Purpose of the Study:

• To develop novel human anti-HIV-1 single-chain variable fragments (scFvs) targeting the conserved CD4 binding site (CD4bs).
• To evaluate the neutralizing activity of these scFvs against pediatric HIV-1 strains, particularly subtype C.
• To explore the potential of these scFvs as therapeutic agents for pediatric HIV-1 passive immunotherapy.

Main Methods:

• Construction of a human anti-HIV-1 scFv phage library from pediatric cross-neutralizers.
• Biopanning the library using a CD4bs-specific antigen (RSC3 core protein).
• Characterization of identified scFvs for neutralizing breadth, potency, and epitope specificity (competition with VRC01).

Main Results:

• Two cross-neutralizing scFv monoclonals, 2B10 and 2E4, were identified.
• 2B10 demonstrated 77% neutralizing breadth against 49 viruses with a GMT of 17.9 µg/ml.
• Both scFvs targeted the CD4bs, with 2B10 showing efficacy against pediatric subtype C and A viruses.

Conclusions:

• The identified CD4bs-directed scFvs (2B10 and 2E4) are potent neutralizers of HIV-1, including pediatric strains.
• These scFvs represent promising candidates for passive immunotherapy against HIV-1.
• Combining these scFvs with antiretroviral drugs may effectively suppress viremia and prevent disease progression in children.