Neutralization profiles of HIV-1 viruses from the VRC01 Antibody Mediated Prevention (AMP) trials.
The VRC01 Antibody Mediated Prevention (AMP) efficacy trials conducted between 2016 and 2020 showed for the first time that passively administered broadly neutralizing antibodies (bnAbs) could prevent HIV-1 acquisition against bnAb-sensitive viruses. HIV-1 viruses isolated from AMP participants who...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-06-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011469&type=printable |
| _version_ | 1797676533593145344 |
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| author | Nonhlanhla N Mkhize Anna E J Yssel Haajira Kaldine Rebecca T van Dorsten Amanda S Woodward Davis Nicolas Beaume David Matten Bronwen Lambson Tandile Modise Prudence Kgagudi Talita York Dylan H Westfall Elena E Giorgi Bette Korber Colin Anthony Rutendo E Mapengo Valerie Bekker Elizabeth Domin Amanda Eaton Wenjie Deng Allan DeCamp Yunda Huang Peter B Gilbert Asanda Gwashu-Nyangiwe Ruwayhida Thebus Nonkululeko Ndabambi Dieter Mielke Nyaradzo Mgodi Shelly Karuna Srilatha Edupuganti Michael S Seaman Lawrence Corey Myron S Cohen John Hural M Juliana McElrath James I Mullins David Montefiori Penny L Moore Carolyn Williamson Lynn Morris |
| author_facet | Nonhlanhla N Mkhize Anna E J Yssel Haajira Kaldine Rebecca T van Dorsten Amanda S Woodward Davis Nicolas Beaume David Matten Bronwen Lambson Tandile Modise Prudence Kgagudi Talita York Dylan H Westfall Elena E Giorgi Bette Korber Colin Anthony Rutendo E Mapengo Valerie Bekker Elizabeth Domin Amanda Eaton Wenjie Deng Allan DeCamp Yunda Huang Peter B Gilbert Asanda Gwashu-Nyangiwe Ruwayhida Thebus Nonkululeko Ndabambi Dieter Mielke Nyaradzo Mgodi Shelly Karuna Srilatha Edupuganti Michael S Seaman Lawrence Corey Myron S Cohen John Hural M Juliana McElrath James I Mullins David Montefiori Penny L Moore Carolyn Williamson Lynn Morris |
| author_sort | Nonhlanhla N Mkhize |
| collection | DOAJ |
| description | The VRC01 Antibody Mediated Prevention (AMP) efficacy trials conducted between 2016 and 2020 showed for the first time that passively administered broadly neutralizing antibodies (bnAbs) could prevent HIV-1 acquisition against bnAb-sensitive viruses. HIV-1 viruses isolated from AMP participants who acquired infection during the study in the sub-Saharan African (HVTN 703/HPTN 081) and the Americas/European (HVTN 704/HPTN 085) trials represent a panel of currently circulating strains of HIV-1 and offer a unique opportunity to investigate the sensitivity of the virus to broadly neutralizing antibodies (bnAbs) being considered for clinical development. Pseudoviruses were constructed using envelope sequences from 218 individuals. The majority of viruses identified were clade B and C; with clades A, D, F and G and recombinants AC and BF detected at lower frequencies. We tested eight bnAbs in clinical development (VRC01, VRC07-523LS, 3BNC117, CAP256.25, PGDM1400, PGT121, 10-1074 and 10E8v4) for neutralization against all AMP placebo viruses (n = 76). Compared to older clade C viruses (1998-2010), the HVTN703/HPTN081 clade C viruses showed increased resistance to VRC07-523LS and CAP256.25. At a concentration of 1μg/ml (IC80), predictive modeling identified the triple combination of V3/V2-glycan/CD4bs-targeting bnAbs (10-1074/PGDM1400/VRC07-523LS) as the best against clade C viruses and a combination of MPER/V3/CD4bs-targeting bnAbs (10E8v4/10-1074/VRC07-523LS) as the best against clade B viruses, due to low coverage of V2-glycan directed bnAbs against clade B viruses. Overall, the AMP placebo viruses represent a valuable resource for defining the sensitivity of contemporaneous circulating viral strains to bnAbs and highlight the need to update reference panels regularly. Our data also suggests that combining bnAbs in passive immunization trials would improve coverage of global viruses. |
| first_indexed | 2024-03-11T22:29:33Z |
| format | Article |
| id | doaj.art-1a870a5047ec41f0af5508300c65082a |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-03-11T22:29:33Z |
| publishDate | 2023-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-1a870a5047ec41f0af5508300c65082a2023-09-23T05:30:46ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-06-01196e101146910.1371/journal.ppat.1011469Neutralization profiles of HIV-1 viruses from the VRC01 Antibody Mediated Prevention (AMP) trials.Nonhlanhla N MkhizeAnna E J YsselHaajira KaldineRebecca T van DorstenAmanda S Woodward DavisNicolas BeaumeDavid MattenBronwen LambsonTandile ModisePrudence KgagudiTalita YorkDylan H WestfallElena E GiorgiBette KorberColin AnthonyRutendo E MapengoValerie BekkerElizabeth DominAmanda EatonWenjie DengAllan DeCampYunda HuangPeter B GilbertAsanda Gwashu-NyangiweRuwayhida ThebusNonkululeko NdabambiDieter MielkeNyaradzo MgodiShelly KarunaSrilatha EdupugantiMichael S SeamanLawrence CoreyMyron S CohenJohn HuralM Juliana McElrathJames I MullinsDavid MontefioriPenny L MooreCarolyn WilliamsonLynn MorrisThe VRC01 Antibody Mediated Prevention (AMP) efficacy trials conducted between 2016 and 2020 showed for the first time that passively administered broadly neutralizing antibodies (bnAbs) could prevent HIV-1 acquisition against bnAb-sensitive viruses. HIV-1 viruses isolated from AMP participants who acquired infection during the study in the sub-Saharan African (HVTN 703/HPTN 081) and the Americas/European (HVTN 704/HPTN 085) trials represent a panel of currently circulating strains of HIV-1 and offer a unique opportunity to investigate the sensitivity of the virus to broadly neutralizing antibodies (bnAbs) being considered for clinical development. Pseudoviruses were constructed using envelope sequences from 218 individuals. The majority of viruses identified were clade B and C; with clades A, D, F and G and recombinants AC and BF detected at lower frequencies. We tested eight bnAbs in clinical development (VRC01, VRC07-523LS, 3BNC117, CAP256.25, PGDM1400, PGT121, 10-1074 and 10E8v4) for neutralization against all AMP placebo viruses (n = 76). Compared to older clade C viruses (1998-2010), the HVTN703/HPTN081 clade C viruses showed increased resistance to VRC07-523LS and CAP256.25. At a concentration of 1μg/ml (IC80), predictive modeling identified the triple combination of V3/V2-glycan/CD4bs-targeting bnAbs (10-1074/PGDM1400/VRC07-523LS) as the best against clade C viruses and a combination of MPER/V3/CD4bs-targeting bnAbs (10E8v4/10-1074/VRC07-523LS) as the best against clade B viruses, due to low coverage of V2-glycan directed bnAbs against clade B viruses. Overall, the AMP placebo viruses represent a valuable resource for defining the sensitivity of contemporaneous circulating viral strains to bnAbs and highlight the need to update reference panels regularly. Our data also suggests that combining bnAbs in passive immunization trials would improve coverage of global viruses.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011469&type=printable |
| spellingShingle | Nonhlanhla N Mkhize Anna E J Yssel Haajira Kaldine Rebecca T van Dorsten Amanda S Woodward Davis Nicolas Beaume David Matten Bronwen Lambson Tandile Modise Prudence Kgagudi Talita York Dylan H Westfall Elena E Giorgi Bette Korber Colin Anthony Rutendo E Mapengo Valerie Bekker Elizabeth Domin Amanda Eaton Wenjie Deng Allan DeCamp Yunda Huang Peter B Gilbert Asanda Gwashu-Nyangiwe Ruwayhida Thebus Nonkululeko Ndabambi Dieter Mielke Nyaradzo Mgodi Shelly Karuna Srilatha Edupuganti Michael S Seaman Lawrence Corey Myron S Cohen John Hural M Juliana McElrath James I Mullins David Montefiori Penny L Moore Carolyn Williamson Lynn Morris Neutralization profiles of HIV-1 viruses from the VRC01 Antibody Mediated Prevention (AMP) trials. PLoS Pathogens |
| title | Neutralization profiles of HIV-1 viruses from the VRC01 Antibody Mediated Prevention (AMP) trials. |
| title_full | Neutralization profiles of HIV-1 viruses from the VRC01 Antibody Mediated Prevention (AMP) trials. |
| title_fullStr | Neutralization profiles of HIV-1 viruses from the VRC01 Antibody Mediated Prevention (AMP) trials. |
| title_full_unstemmed | Neutralization profiles of HIV-1 viruses from the VRC01 Antibody Mediated Prevention (AMP) trials. |
| title_short | Neutralization profiles of HIV-1 viruses from the VRC01 Antibody Mediated Prevention (AMP) trials. |
| title_sort | neutralization profiles of hiv 1 viruses from the vrc01 antibody mediated prevention amp trials |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011469&type=printable |
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