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

Christoph Kreer, Cosimo Lupo, Meryem S. Ercanoglu, Lutz Gieselmann, Natanael Spisak, Jan Grossbach, Maike Schlotz, Philipp Schommers, Henning Gruell, Leona Dold, Andreas Beyer, Armita Nourmohammad, Thierry Mora, Aleksandra M. Walczak and Florian Klein ()
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Christoph Kreer: University of Cologne
Cosimo Lupo: PSL University, Sorbonne Université, and Université Paris Cité
Meryem S. Ercanoglu: University of Cologne
Lutz Gieselmann: University of Cologne
Natanael Spisak: PSL University, Sorbonne Université, and Université Paris Cité
Jan Grossbach: University of Cologne
Maike Schlotz: University of Cologne
Philipp Schommers: University of Cologne
Henning Gruell: University of Cologne
Leona Dold: University Hospital of Bonn
Andreas Beyer: University of Cologne
Armita Nourmohammad: Max Planck Institute for Dynamics and Self-Organization
Thierry Mora: PSL University, Sorbonne Université, and Université Paris Cité
Aleksandra M. Walczak: PSL University, Sorbonne Université, and Université Paris Cité
Florian Klein: University of Cologne

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-42906-y

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