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Determining probabilities of HIV-1 bNAb development in healthy and chronically infected individuals
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Abstract HIV-1 broadly neutralizing antibodies (bNAbs) are able to suppress viremia and prevent infection. Their induction by vaccination is therefore a major goal. However, in contrast to antibodies that neutralize other pathogens, HIV-1-specific bNAbs frequently carry uncommon molecular characteristics that might prevent their induction. Here, we performed unbiased sequence analyses of B cell receptor repertoires from 57 healthy and 46 chronically HIV-1- or HCV-infected individuals and learned probabilistic models to predict the likelihood of bNAb development. We show that lower probabilities for bNAbs are predictive of higher HIV-1 neutralization activity. Moreover, ranking of bNAbs by their probabilities allowed to identify highly potent antibodies with superior generation probabilities as preferential targets for vaccination approaches. Importantly, we found equal bNAb probabilities across infected and healthy donors. This implies that chronic infection is not a prerequisite for the generation of bNAbs, fostering the hope that HIV-1 vaccines can induce bNAb development in healthy individuals.
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