Next-generation bNAbs for HIV-1 cure strategies

Schriek, A.I.; Aldon, Y.L.T.; van Gils, M.J.; de Taeye, S.W.

doi:10.1016/j.antiviral.2023.105788

Cited by 5 publications

(6 citation statements)

References 247 publications

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“…While both steps represent an important research effort, the process has benefited from identified immune donors 19 and the development of high-throughput analyses of antibody repertoires by next-generation sequencing (NGS). Still, the number of identified HIV bNAbs remains relatively low, with only 255 of them being reported 3 , 20 . Some bNAbs have been investigated in registered clinical trials, for prevention, as a component of long-acting antiretroviral therapy (ART), or intervention aimed at long-term drug-free remission of HIV 17 , 21 , 22 .…”

Section: Introductionmentioning

confidence: 99%

RAIN: machine learning-based identification for HIV-1 bNAbs

Foglierini,

Nortier,

Schelling

et al. 2024

Nat Commun

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Broadly neutralizing antibodies (bNAbs) are promising candidates for the treatment and prevention of HIV-1 infections. Despite their critical importance, automatic detection of HIV-1 bNAbs from immune repertoires is still lacking. Here, we develop a straightforward computational method for the Rapid Automatic Identification of bNAbs (RAIN) based on machine learning methods. In contrast to other approaches, which use one-hot encoding amino acid sequences or structural alignment for prediction, RAIN uses a combination of selected sequence-based features for the accurate prediction of HIV-1 bNAbs. We demonstrate the performance of our approach on non-biased, experimentally obtained and sequenced BCR repertoires from HIV-1 immune donors. RAIN processing leads to the successful identification of distinct HIV-1 bNAbs targeting the CD4-binding site of the envelope glycoprotein. In addition, we validate the identified bNAbs using an in vitro neutralization assay and we solve the structure of one of them in complex with the soluble native-like heterotrimeric envelope glycoprotein by single-particle cryo-electron microscopy (cryo-EM). Overall, we propose a method to facilitate and accelerate HIV-1 bNAbs discovery from non-selected immune repertoires.

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Section: Introductionmentioning

confidence: 99%

RAIN: machine learning-based identification for HIV-1 bNAbs

Foglierini,

Nortier,

Schelling

et al. 2024

Nat Commun

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“…Additionally, the density of Env expressed on reactivated HIV-1-infected cells remains low, further emphasizing the need for highly effective antibodies in antibody-mediated immunotherapy [ 16 ]. (4) Fourth, ART successfully suppresses viral replication and prevents disease progression; however, it is unable to reach and eradicate the proviral reservoir or boost host antiviral immunity [ 17 ]. Consequently, because the proviral reservoir remains unaffected by ART, strict daily and lifelong adherence is necessary to prevent viral rebound.…”

Section: Introductionmentioning

confidence: 99%

“…These antibodies, termed ‘broadly neutralizing antibodies’ (bNAbs), target conserved regions on the trimeric envelope glycoprotein found on the surface of HIV-1. The Env proteins are the only viral protein expressed on the surface of HIV-1 and are covered by a highly dense glycan shield [ 17 , 22 , 23 ], rapidly shifting glycans that shield potential target sites from neutralization by antibodies but not receptor binding. In other words, the glycan shield facilitates the evasion of the immune system [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

The Use of Broadly Neutralizing Antibodies (bNAbs) in HIV-1 Treatment and Prevention

Thavarajah,

Hønge,

Wejse

2024

Viruses

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Background: Although antiretroviral therapy (ART) effectively halts disease progression in HIV infection, the complete eradication of the virus remains elusive. Additionally, challenges such as long-term ART toxicity, drug resistance, and the demanding regimen of daily and lifelong adherence required by ART highlight the imperative need for alternative therapeutic and preventative approaches. In recent years, broadly neutralizing antibodies (bNAbs) have emerged as promising candidates, offering potential for therapeutic, preventative, and possibly curative interventions against HIV infection. Objective: This review aims to provide a comprehensive overview of the current state of knowledge regarding the passive immunization of bNAbs in HIV-1-infected individuals. Main findings: Recent findings from clinical trials have highlighted the potential of bNAbs in the treatment, prevention, and quest for an HIV-1 cure. While monotherapy with a single bNAb is insufficient in maintaining viral suppression and preventing viral escape, ultimately leading to viral rebound, combination therapy with potent, non-overlapping epitope-targeting bNAbs have demonstrated prolonged viral suppression and delayed time to rebound by effectively restricting the emergence of escape mutations, albeit largely in individuals with bNAb-sensitive strains. Additionally, passive immunization with bNAb has provided a “proof of concept” for antibody-mediated prevention against HIV-1 acquisition, although complete prevention has not been obtained. Therefore, further research on the use of bNAbs in HIV-1 treatment and prevention remains imperative.

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“…Still, the number of identi ed HIV bNAbs remains relatively low, with only 250 of them reported 3,20 . Some bNAbs have been investigated in registered clinical trials, for prevention, as a component of long-acting antiretroviral therapy (ART), or as a component of intervention aimed at long-term drug-free remission of HIV 17,21,22 .…”

mentioning

confidence: 99%

“…While both steps represent an important research effort, the process has beneficiated from identified immune donors 19 and the development of high-throughput analyses of antibody repertoires by next-generation sequencing ( NGS ). Still, the number of identified HIV bNAbs remains relatively low, with only 250 of them reported 3 , 20 . Some bNAbs have been investigated in registered clinical trials, for prevention, as a component of long-acting antiretroviral therapy (ART), or as a component of intervention aimed at long-term drug-free remission of HIV 17 , 21 , 22 .…”

mentioning

confidence: 99%

RAIN: a Machine Learning-based identification for HIV-1 bNAbs

Perez,

Foglierini

2024

Preprint

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Broadly neutralizing antibodies (bNAbs) are promising candidates for the treatment and prevention of HIV-1 infection. Despite their critical importance, automatic detection of HIV-1 bNAbs from immune repertoire is still lacking. Here, we developed a straightforward computational method for Rapid Automatic Identification of bNAbs (RAIN) based on Machine Learning methods. In contrast to other approaches using one-hot encoding amino acid sequences or structural alignment for prediction, RAIN uses a combination of selected sequence-based features for accurate prediction of HIV-1 bNAbs. We demonstrate the performance of our approach on non-biased, experimentally obtained sequenced BCR repertoires from HIV-1 immune donors. RAIN processing leads to the successful identification of novel HIV-1 bNAbs targeting the CD4-binding site of the envelope glycoprotein. In addition, we validate the identified bNAbs using in vitro neutralization assay and we solve the structure of one of them in complex with the soluble native-like heterotrimeric envelope glycoprotein by single-particle cryo-electron microscopy (cryo-EM). Overall, we propose a method to facilitate and accelerate HIV-1 bNAbs discovery from non-selected immune repertoires.

show abstract

Next-generation bNAbs for HIV-1 cure strategies

Cited by 5 publications

References 247 publications

RAIN: machine learning-based identification for HIV-1 bNAbs

RAIN: machine learning-based identification for HIV-1 bNAbs

The Use of Broadly Neutralizing Antibodies (bNAbs) in HIV-1 Treatment and Prevention

RAIN: a Machine Learning-based identification for HIV-1 bNAbs

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