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Journal Article

Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals

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Nourmohammad,  Armita
Max Planck Research Group Statistical physics of evolving systems, Max Planck Institute for Dynamics and Self-Organization, Max Planck Society;

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Citation

Kreer, C., Lupo, C., Ercanoglu, M., Gieselmann, L., Spisak, N., Grossbach, J., et al. (2023). Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals. Nature Communications, 14(1): 7137. doi:10.1038/s41467-023-42906-y.


Cite as: https://hdl.handle.net/21.11116/0000-000E-0BE3-6
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 perform unbiased sequence analyses of B cell receptor repertoires from 57 uninfected and 46 chronically HIV-1- or HCV-infected individuals and learn probabilistic models to predict the likelihood of bNAb development. We formally show that lower probabilities for bNAbs are predictive of higher HIV-1 neutralization activity. Moreover, ranking bNAbs by their probabilities allows to identify highly potent antibodies with superior generation probabilities as preferential targets for vaccination approaches. Importantly, we find equal bNAb probabilities across infected and uninfected individuals. 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 uninfected people.