Fig. 1: Visual representation of how two independent pieces of information (serum bnAb concentration at a given time point and neutralization sensitivity of a target virus to the bnAb (IC₈₀)) are used to calculate the PT₈₀ biomarker.

a, Formula for calculation of PT₈₀ for a bnAb against a target virus. IC₈₀ for a clinical lot bnAb product against a target virus, as determined by the TZM-bl target cell assay, is the bnAb concentration needed for 80% reduction in RLU compared with target virus control wells after subtraction of background RLU. Based on the PT₈₀ biomarker, increasing bnAb serum concentration and increasing target virus sensitivity (that is, decreasing IC₈₀) have an equal impact on increasing PT₈₀ and hence improvement in potential prevention efficacy. b, Example calculations showing how PT₈₀ against a target virus differs for three different bnAbs sharing the same IC₈₀ against the target virus yet are present at different serum concentrations. A similar result would be obtained (differing PT₈₀ values) if the same bnAb was present at three different serum concentrations. c, Adaptation of the formula shown in a to a scenario where average PT₈₀ is calculated against a population of exposing viruses. d, Example calculations of average PT₈₀ over a follow-up period against an exposing virus population for three different bnAbs. The yellow bnAb has characteristics of VRC01 observed in the AMP trials (average serum concentration over VRC01 recipients and over 80 weeks of follow-up 20 µg ml^–1, average IC₈₀ of exposing viruses 4.0 µg ml^–1, which is calculated as the weighted average of the three IC₈₀s: for example, (0.5 µg ml^–1) × 0.30 + (2.0 µg ml^–1) × 0.15 + (6.5 µg ml^–1) × 0.55 = 4.0 µg ml^–1). If IC₈₀ is used for comparison of the yellow and blue bnAbs, the results indicate that the blue bnAb is twofold better than the yellow in regard to its potential prevention efficacy, whereas if PT₈₀ is used for comparison the blue bnAb is fivefold better than the yellow. The PT₈₀ biomarker is superior on account of its enhanced measurement of neutralization potency against anticipated exposing viruses.