Current methods for detecting and assessing HIV-1 antibody resistance
Antiretroviral therapy is the standard treatment for HIV, but it requires daily use and can cause side effects. Despite being available for decades, there are still 1.5 million new infections and 700,000 deaths each year, highlighting the need for better therapies. Broadly neutralizing antibodies (b...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1443377/full |
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| author | Stanley Odidika Stanley Odidika Stanley Odidika Martin Pirkl Martin Pirkl Thomas Lengauer Thomas Lengauer Thomas Lengauer Philipp Schommers Philipp Schommers Philipp Schommers |
| author_facet | Stanley Odidika Stanley Odidika Stanley Odidika Martin Pirkl Martin Pirkl Thomas Lengauer Thomas Lengauer Thomas Lengauer Philipp Schommers Philipp Schommers Philipp Schommers |
| author_sort | Stanley Odidika |
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| description | Antiretroviral therapy is the standard treatment for HIV, but it requires daily use and can cause side effects. Despite being available for decades, there are still 1.5 million new infections and 700,000 deaths each year, highlighting the need for better therapies. Broadly neutralizing antibodies (bNAbs), which are highly active against HIV-1, represent a promising new approach and clinical trials have demonstrated the potential of bNAbs in the treatment and prevention of HIV-1 infection. However, HIV-1 antibody resistance (HIVAR) due to variants in the HIV-1 envelope glycoproteins (HIV-1 Env) is not well understood yet and poses a critical problem for the clinical use of bNAbs in treatment. HIVAR also plays an important role in the future development of an HIV-1 vaccine, which will require elicitation of bNAbs to which the circulating strains are sensitive. In recent years, a variety of methods have been developed to detect, characterize and predict HIVAR. Structural analysis of antibody-HIV-1 Env complexes has provided insight into viral residues critical for neutralization, while testing of viruses for antibody susceptibility has verified the impact of some of these residues. In addition, in vitro viral neutralization and adaption assays have shaped our understanding of bNAb susceptibility based on the envelope sequence. Furthermore, in vivo studies in animal models have revealed the rapid emergence of escape variants to mono- or combined bNAb treatments. Finally, similar variants were found in the first clinical trials testing bNAbs for the treatment of HIV-1-infected patients. These structural, in vitro, in vivo and clinical studies have led to the identification and validation of HIVAR for almost all available bNAbs. However, defined assays for the detection of HIVAR in patients are still lacking and for some novel, highly potent and broad-spectrum bNAbs, HIVAR have not been clearly defined. Here, we review currently available approaches for the detection, characterization and prediction of HIVAR. |
| format | Article |
| id | doaj-art-0c783eef5a6b443b8b8f11b8cf4e24e5 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-0c783eef5a6b443b8b8f11b8cf4e24e52025-01-06T06:59:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14433771443377Current methods for detecting and assessing HIV-1 antibody resistanceStanley Odidika0Stanley Odidika1Stanley Odidika2Martin Pirkl3Martin Pirkl4Thomas Lengauer5Thomas Lengauer6Thomas Lengauer7Philipp Schommers8Philipp Schommers9Philipp Schommers10Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyCenter for Molecular Medicine Cologne (CMMC), Cologne, GermanyGerman Center for Infection Research (DZIF), Partner Site Cologne-Bonn, Cologne, GermanyGerman Center for Infection Research (DZIF), Partner Site Cologne-Bonn, Cologne, GermanyInstitute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyGerman Center for Infection Research (DZIF), Partner Site Cologne-Bonn, Cologne, GermanyInstitute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyMax Planck Institute for Informatics and Saarland Informatics Campus, Saarbrücken, GermanyDepartment I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanyCenter for Molecular Medicine Cologne (CMMC), Cologne, GermanyGerman Center for Infection Research (DZIF), Partner Site Cologne-Bonn, Cologne, GermanyAntiretroviral therapy is the standard treatment for HIV, but it requires daily use and can cause side effects. Despite being available for decades, there are still 1.5 million new infections and 700,000 deaths each year, highlighting the need for better therapies. Broadly neutralizing antibodies (bNAbs), which are highly active against HIV-1, represent a promising new approach and clinical trials have demonstrated the potential of bNAbs in the treatment and prevention of HIV-1 infection. However, HIV-1 antibody resistance (HIVAR) due to variants in the HIV-1 envelope glycoproteins (HIV-1 Env) is not well understood yet and poses a critical problem for the clinical use of bNAbs in treatment. HIVAR also plays an important role in the future development of an HIV-1 vaccine, which will require elicitation of bNAbs to which the circulating strains are sensitive. In recent years, a variety of methods have been developed to detect, characterize and predict HIVAR. Structural analysis of antibody-HIV-1 Env complexes has provided insight into viral residues critical for neutralization, while testing of viruses for antibody susceptibility has verified the impact of some of these residues. In addition, in vitro viral neutralization and adaption assays have shaped our understanding of bNAb susceptibility based on the envelope sequence. Furthermore, in vivo studies in animal models have revealed the rapid emergence of escape variants to mono- or combined bNAb treatments. Finally, similar variants were found in the first clinical trials testing bNAbs for the treatment of HIV-1-infected patients. These structural, in vitro, in vivo and clinical studies have led to the identification and validation of HIVAR for almost all available bNAbs. However, defined assays for the detection of HIVAR in patients are still lacking and for some novel, highly potent and broad-spectrum bNAbs, HIVAR have not been clearly defined. Here, we review currently available approaches for the detection, characterization and prediction of HIVAR.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1443377/fullHIVantibodymutationaidsbNAbsbroadly neutralizing antibodies |
| spellingShingle | Stanley Odidika Stanley Odidika Stanley Odidika Martin Pirkl Martin Pirkl Thomas Lengauer Thomas Lengauer Thomas Lengauer Philipp Schommers Philipp Schommers Philipp Schommers Current methods for detecting and assessing HIV-1 antibody resistance Frontiers in Immunology HIV antibody mutation aids bNAbs broadly neutralizing antibodies |
| title | Current methods for detecting and assessing HIV-1 antibody resistance |
| title_full | Current methods for detecting and assessing HIV-1 antibody resistance |
| title_fullStr | Current methods for detecting and assessing HIV-1 antibody resistance |
| title_full_unstemmed | Current methods for detecting and assessing HIV-1 antibody resistance |
| title_short | Current methods for detecting and assessing HIV-1 antibody resistance |
| title_sort | current methods for detecting and assessing hiv 1 antibody resistance |
| topic | HIV antibody mutation aids bNAbs broadly neutralizing antibodies |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1443377/full |
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