Autologous neutralizing responses can develop to high potency after a single boost, whereas the broad FP-directed response generally develop more slowly, requiring multiple boosts.

A. Autologous neutralizing response increased to high titer while heterologous neutralizing response (calculated from the geometric mean of the 18 heterologous strains in Figs 1B and 2C) developed more slowly from week 28 to week 56. Strains with a value of “<20” were excluded from geometric mean calculation. B. Autologous neutralizing responses were more potent than heterologous responses. C. Potential mechanistic explanations for the more rapid increase and higher overall titer of autologous neutralizing responses [atomic-level analyses were not possible for glycan-hole directed antibodies, as structural definition of their interactions have only been determined at low resolution (e.g. [20])].