HIV bnAb Germline Maturation Simulator

Vaccine Regimen Design Phase 1 Active

Clinical Trial Presets

1. Germline Prime (Day 0)

2. Shepherding Boost 1 (Wk 8)

3. Native Polisher Boost 2 (Wk 20)

Selection Stringency (Tfh Help): 78%

Precursor Frequency (per million): 1.2

Immunological Rationale: Rare naive B cells harboring VRC01-class VH1-2 germline genes have zero affinity for native HIV envelopes due to loop steric clashes. Germline-targeting prime activates these 1-in-a-million precursors; subsequent engineered shepherding trims guide mutations toward cross-clade recognition.

Germinal Center Follicle (Lymph Node)

Dark Zone (Somatic Mutation) ⇄ Light Zone (FDC Selection)

Active bnAb Clones

SHM Divergence

18.4%

Global Breadth

88.9%

Mean Potency (IC50)

0.14 µg/mL

Rare Germline Precursor

Somatically Hypermutated

Broadly Neutralizing (bnAb)

Apoptotic / Outcompeted

FDC Antigen Complex

18-Strain HIV Pseudovirus Panel Tier-2 Sensitive

Clonal Phylogeny & CDR Divergence

Cross-Clade Breadth: Neutralizing Tier-2 clinical isolates (Clades A, B, C, AE, AG) requires ~15-20% SHM divergence with critical CDRL1 5-amino-acid deletion and CDRH3 contact stabilization.