bnAb Lineage Steering: HIV Vaccine Immunogen Simulator

Vaccine Regimen Preset NATURE 2026 BENCHMARK

Sequential Germline Prime-Boost ★ Clinical

eOD-GT8 60mer prime expands rare naive VRC01-class precursors → Core-g28v2 intermediate boost → Native BG505 Trimer polish.

Standard Monovalent Trimer Stalled

Direct native BG505 trimer immunization. Clones fail to engage rare germline precursors due to steric glycan shield entrapment.

Accelerated / Off-Target Boost Diverged

High antigen dosing without affinity-stepping causes off-target non-neutralizing immunodominant diversion (V3 loop decoy).

Immunization Stages Dose 0 of 3

Germinal Center Selection Stringency High (85%)

Somatic Hypermutation (SHM) Rate 2.8 mut/cycle

Naive Precursor Frequency 1 in 300,000 (0.0003%)

Clonal Lineage Maturation Tree & Fitness Trajectory

Clones: 1 | Active Lineages: 1

Germline Precursor (VH1-2*02)

Intermediate Mutants

Broadly Neutralizing Lineage (VRC01-like)

Off-Target / Non-Neutralizing Decoy

Node size = Clonal Population | Ring = Binding Affinity

Affinity Maturation Kinetics & Mutational Distance

Target Epitope: CD4-Binding Site (CD4bs)

Global HIV-1 Pseudovirus Panel (12-Strain) 0% Breadth

Neutralization Breadth

> 50 µg/mL

Geometric Mean IC50

12,400 nM

Lead Affinity (Kd)

0.0%

VH Mutation Divergence

Clade A (3) Clade B (3) Clade C (4) Circulating Rec (2)

Lead Clone CDR & Structural Mutation Inspector Clone #1 (Germline)

VH Gene Allele IGHV1-2*02 / IGHD / IGHJ2

CDRH1 Loop

No mutations

CDRH2 Loop (Trp50/Asn58)

Germline configuration

CDRH3 (5-aa Length Match)

Germline ARDGS

CDRL3 (Short 5-aa deletion)

Standard length (8 aa)

Key bnAb Enablers

None detected

The Science of Germline-Targeting HIV Vaccines