Journal Article

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

Gruell, Henning, Dold, Leona, Grossbach, Jan, Schlotz, Maike, Ercanoglu, Meryem S., Beyer, Andreas, Gieselmann, Lutz, Lupo, Cosimo, Walczak, Aleksandra M., Kreer, Christoph, Spisak, Natanael, Mora, Thierry, Nourmohammad, Armita, Klein, Florian, Schommers, Philipp

2023

Overview

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. Successful induction of broadly neutralizing antibodies is a main challenge in HIV vaccine development. The authors provide a framework to determine probabilities of antibody sequence development and show that uninfected and chronically infected individuals have the same chances to develop HIV-1 neutralizing antibodies.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 45 / 45/23 / 45/77 / 631/114/2397 / 631/250/2152 / 631/250/255/1901 / 82/1 / AIDS Vaccines / Antibodies / Antibodies, Neutralizing / Broadly Neutralizing Antibodies / Chronic infection / HIV / HIV Antibodies / HIV Infections / HIV-1 / Human immunodeficiency virus / Humanities and Social Sciences / Humans / Immunization / Life Sciences / Mathematical models / multidisciplinary / Neutralization / Neutralizing / Probabilistic models / Science / Science (multidisciplinary) / Vaccine development / Vaccines / Viremia