An earlier study had provided direct evidence for the hypothesis that filling rare glycan holes could enable escape from glycan hole-targeting NAbs in natural infections: a hole near position 295 in subject CH40’s TF (Figure 3A) was filled over time, a change that reduced the TF sensitivity by 4.3- to 5.2-fold to 4- and 6-month plasma (Bar et al., 2012). The gene discussed is TF; the disease is infection.