Determinants of HIV-1 broadly neutralizing antibody induction

Author(s): Peter Rusert [1]; Roger D Kouyos [1, 2]; Claus Kadelka [1, 2]; Hanna Ebner [1]; Merle Schanz [1]; Michael Huber [1]; Dominique L Braun [1, 2]; Nathanael Hozé [3]; [...]
Broadly neutralizing antibodies (bnAbs) are a focal component of HIV-1 vaccine design, yet basic aspects of their induction remain poorly understood. Here we report on viral, host and disease factors that steer bnAb evolution using the results of a systematic survey in 4,484 HIV-1-infected individuals that identified 239 bnAb inducers. We show that three parameters that reflect the exposure to antigen--viral load, length of untreated infection and viral diversity--independently drive bnAb evolution. Notably, black participants showed significantly (P = 0.0086-0.038) higher rates of bnAb induction than white participants. Neutralization fingerprint analysis, which was used to delineate plasma specificity, identified strong virus subtype dependencies, with higher frequencies of CD4-binding-site bnAbs in infection with subtype B viruses (P = 0.02) and higher frequencies of V2-glycan-specific bnAbs in infection with non-subtype B viruses (P = 1 x 10[sup.-5]). Thus, key host, disease and viral determinants, including subtype-specific envelope features that determine bnAb specificity, remain to be unraveled and harnessed for bnAb-based vaccine design.