Shared Maturation Pathways of HIV-1 Envelope-reactive V3-glycan bnAb Lineages in Human and Rhesus Macaque

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Understanding broadly neutralizing antibody (bnAb) development is crucial for designing effective HIV-1 vaccines.
• Rhesus macaques (RMs) infected with Simian-HIV (SHIV) serve as a model to study antibody lineage development.

Purpose of the Study:

• To analyze HIV-1 envelope-antibody coevolution in RMs infected with SHIV.
• To compare bnAb lineage development in RMs with known human bnAb lineages.

Main Methods:

• Analysis of HIV-1 envelope-antibody coevolution in 18 RMs infected with SHIV.BG505.
• Isolation and characterization of a bnAb lineage (DH1030) from an RM.
• Genetic, functional, and structural comparison of macaque-derived DH1030 with human-derived DH270 bnAb lineages.

Main Results:

• Conserved patterns of antibody recognition and Env escape were observed in RMs.
• A single clonal bnAb lineage (DH1030) targeting V3-glycan was isolated from an RM.
• Macaque DH1030 and human DH270 bnAbs shared improbable mutations in HCDR2 critical for development.

Conclusions:

• Key mutations and convergent antibody evolution patterns are shared across primate species and HIV-1 subtypes.
• These findings suggest a common bnAb maturation pathway applicable to HIV-1 vaccine design.