Development of Neutralization Breadth against Diverse HIV-1 by Increasing Ab-Ag Interface on V2.

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Understanding broadly neutralizing antibodies (bnAbs) against HIV-1 is crucial for vaccine development.
• Identifying maturation pathways of bnAbs can inform novel vaccine strategies.

Purpose of the Study:

• To investigate the maturation pathway of the J038 bnAb lineage derived from a SHIV-infected macaque.
• To understand the structural and functional features of J038 bnAbs for HIV-1 vaccine design.

Main Methods:

• Isolation and characterization of the J038 bnAb lineage from a long-term SHIV-infected macaque.
• Analysis of antibody binding to the HIV-1 envelope glycoprotein, including V2 loop conformation and glycan dependence.
• Assessment of neutralization breadth and potency against global HIV-1 strains.

Main Results:

• The J038 lineage bnAbs neutralize 54% of global HIV-1 strains.
• J038 binding induces a unique "up" conformation of the V2 loop and is highly glycan-dependent.
• Continuous maturation expands antibody-Env contact, enhancing neutralization potency and breadth.

Conclusions:

• The J038 lineage provides insights into bnAb maturation pathways.
• This study reveals a novel pathway for eliciting and maturing V2-targeting bnAbs for HIV-1 vaccine development.