HIV bnAb Germline Targeting Simulator

Sequential Regimen Cycle 0/45

STAGE 1: GERMLINE PRIME Wk 0

Immunogen Target

GC Rounds15

STAGE 2: INTERMEDIATE BOOST Wk 8

Intermediate Trimer

GC Rounds15

STAGE 3: POLISHING NATIVE BOOST Wk 16

Polishing Trimer

GC Rounds15

Rare Precursor Recruited: ~1 in 300,000 human naive B-cells possess the unmutated VRC01-class germline genes (VH1-2*02 + 5-aa CDRL3). Germline prime selectively expands this ultra-rare clone.

Germinal Center Somatic Hypermutation & Paratope Docking Ready

Stage: Prime (eOD-GT8)

B-Cell Precursor Affinity: KD: 1.2 μM

CD4bs Glycan Clash: Resolved (94.2%)

Germline Engagement Rate

98.4%

Mean Somatic Mutations

18.6 aa mutations

Glycan Clash Resolution

94.2%

Geometric Mean IC50

0.042 ug/mL

12-Strain Global Panel 91.7% Breadth

Neutralization breadth across difficult Tier-2/3 global isolates (Clades A, B, C, D, CRF01_AE, CRF07_BC):

Lineage Maturation Trajectory

VRC01-Class Heavy Chain (VH1-2)14 mutations

Light Chain Truncation / Flexibility5 mutations

Loop D Insertion AccommodationResolved

Protocol validated: Sequential germline prime-boost achieved 91.7% global HIV neutralization breadth.

Framework: VRC01 / eOD-GT8 60-mer platform | Model: Somatic GC Selection Sim