(GC-arc10) Thresholded Immune State Transitions and Lag Dynamics in Therapeutic Peptide Vaccination for Chronic Hepatitis B A State-Based Statistical Re-analysis of BRII-179

Vaccination outcomes are commonly evaluated using cohort-averaged responses, implic-itly assuming continuous dose–response dynamics. Here, we reanalyse published longitudinaldata from a hepatitis B virus (HBV) peptide vaccination study to examine individual-levelresponse trajectories in both humoral and cellular compartments. Across all treatment arms,antibody responses segregate into discrete responder and non-responder regimes, with sharpthreshold crossings rather than gradual accumulation. Among responders, early divergencefrom non-responders is followed by variable lag phases, yielding clustered activation timesinconsistent with linear kinetics.Co-administration of interferon-α increases the probability and timing of entry into theresponder regime but does not substantially alter post-activation response magnitude, in-dicating modulation of state transition rather than amplification. T-cell responses exhibitanalogous structure, including zero-inflated activation and categorical shifts in antigen recog-nition breadth. Notably, a reproducible transient configuration emerges at week 16 charac-terised by PreS1/PreS2 reactivity in the absence of S-specific responses, resolving by week 20and absent at baseline.Together, these findings support a state-based interpretation of vaccine-induced immu-nity, in which outcomes are governed by transitions between discrete functional regimesrather than monotonic scaling. This perspective provides a unifying explanation for hetero-geneous vaccine responses and suggests that transient response configurations may representinformative intermediate states rather than assay noise or failure.Rather than exhibiting continuous, Gaussian-distributed response magnitudes, immuneoutcomes were dominated by discrete activation states with pronounced lag dynamics, indi-cating threshold-driven state transitions rather than linear accumulation.