Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals
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 characteri...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42906-y |
| _version_ | 1797630138923352064 |
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| author | 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 Florian Klein |
| author_facet | 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 Florian Klein |
| author_sort | Christoph Kreer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T11:03:49Z |
| format | Article |
| id | doaj.art-e900725c8c9741e5a635d16c5aac862f |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-11T11:03:49Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-e900725c8c9741e5a635d16c5aac862f2023-11-12T12:21:52ZengNature PortfolioNature Communications2041-17232023-11-0114111410.1038/s41467-023-42906-yProbabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individualsChristoph Kreer0Cosimo Lupo1Meryem S. Ercanoglu2Lutz Gieselmann3Natanael Spisak4Jan Grossbach5Maike Schlotz6Philipp Schommers7Henning Gruell8Leona Dold9Andreas Beyer10Armita Nourmohammad11Thierry Mora12Aleksandra M. Walczak13Florian Klein14Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of CologneLaboratoire de physique de l’Ecole normale supérieure, CNRS, PSL University, Sorbonne Université, and Université Paris CitéLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of CologneLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of CologneLaboratoire de physique de l’Ecole normale supérieure, CNRS, PSL University, Sorbonne Université, and Université Paris CitéExcellence Cluster on Cellular Stress Responses in Aging Associated Diseases & Institute for Genetics, Faculty of Mathematics and Natural Sciences, University of CologneLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of CologneLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of CologneLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of CologneDepartment of Internal Medicine I, University Hospital of BonnExcellence Cluster on Cellular Stress Responses in Aging Associated Diseases & Institute for Genetics, Faculty of Mathematics and Natural Sciences, University of CologneMax Planck Institute for Dynamics and Self-OrganizationLaboratoire de physique de l’Ecole normale supérieure, CNRS, PSL University, Sorbonne Université, and Université Paris CitéLaboratoire de physique de l’Ecole normale supérieure, CNRS, PSL University, Sorbonne Université, and Université Paris CitéLaboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of CologneAbstract 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.https://doi.org/10.1038/s41467-023-42906-y |
| spellingShingle | 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 Florian Klein Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals Nature Communications |
| title | Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals |
| title_full | Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals |
| title_fullStr | Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals |
| title_full_unstemmed | Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals |
| title_short | Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals |
| title_sort | probabilities of developing hiv 1 bnab sequence features in uninfected and chronically infected individuals |
| url | https://doi.org/10.1038/s41467-023-42906-y |
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