Diverse pathways of escape from all well-characterized VRC01-class broadly neutralizing HIV-1 antibodies.
Many broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus type 1 (HIV-1) were shown effective in animal models, and are currently evaluated in clinical trials. However, use of these antibodies in humans is hampered by the rapid emergence of resistant viruses. Here we show tha...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-08-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC6117093?pdf=render |
| _version_ | 1818526581575909376 |
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| author | Yuka Otsuka Kimberly Schmitt Brian D Quinlan Matthew R Gardner Barnett Alfant Adrian Reich Michael Farzan Hyeryun Choe |
| author_facet | Yuka Otsuka Kimberly Schmitt Brian D Quinlan Matthew R Gardner Barnett Alfant Adrian Reich Michael Farzan Hyeryun Choe |
| author_sort | Yuka Otsuka |
| collection | DOAJ |
| description | Many broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus type 1 (HIV-1) were shown effective in animal models, and are currently evaluated in clinical trials. However, use of these antibodies in humans is hampered by the rapid emergence of resistant viruses. Here we show that soft-randomization can be used to accelerate the parallel identification of viral escape pathways. As a proof of principle, we soft-randomized the epitope regions of VRC01-class bNAbs in replication-competent HIV-1 and selected for resistant variants. After only a few passages, a surprisingly diverse population of antibody-resistant viruses emerged, bearing both novel and previously described escape mutations. We observed that the escape variants resistant to some VRC01-class bNAbs are resistant to most other bNAbs in the same class, and that a subset of variants was completely resistant to every well characterized VRC01-class bNAB, including VRC01, NIH45-46, 3BNC117, VRC07, N6, VRC-CH31, and VRC-PG04. Thus, our data demonstrate that soft randomization is a suitable approach for accelerated detection of viral escape, and highlight the challenges inherent in administering or attempting to elicit VRC01-class antibodies. |
| first_indexed | 2024-12-11T06:25:01Z |
| format | Article |
| id | doaj.art-a8160b611bce49b6a7b475f9f83d8f83 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-11T06:25:01Z |
| publishDate | 2018-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-a8160b611bce49b6a7b475f9f83d8f832022-12-22T01:17:42ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742018-08-01148e100723810.1371/journal.ppat.1007238Diverse pathways of escape from all well-characterized VRC01-class broadly neutralizing HIV-1 antibodies.Yuka OtsukaKimberly SchmittBrian D QuinlanMatthew R GardnerBarnett AlfantAdrian ReichMichael FarzanHyeryun ChoeMany broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus type 1 (HIV-1) were shown effective in animal models, and are currently evaluated in clinical trials. However, use of these antibodies in humans is hampered by the rapid emergence of resistant viruses. Here we show that soft-randomization can be used to accelerate the parallel identification of viral escape pathways. As a proof of principle, we soft-randomized the epitope regions of VRC01-class bNAbs in replication-competent HIV-1 and selected for resistant variants. After only a few passages, a surprisingly diverse population of antibody-resistant viruses emerged, bearing both novel and previously described escape mutations. We observed that the escape variants resistant to some VRC01-class bNAbs are resistant to most other bNAbs in the same class, and that a subset of variants was completely resistant to every well characterized VRC01-class bNAB, including VRC01, NIH45-46, 3BNC117, VRC07, N6, VRC-CH31, and VRC-PG04. Thus, our data demonstrate that soft randomization is a suitable approach for accelerated detection of viral escape, and highlight the challenges inherent in administering or attempting to elicit VRC01-class antibodies.http://europepmc.org/articles/PMC6117093?pdf=render |
| spellingShingle | Yuka Otsuka Kimberly Schmitt Brian D Quinlan Matthew R Gardner Barnett Alfant Adrian Reich Michael Farzan Hyeryun Choe Diverse pathways of escape from all well-characterized VRC01-class broadly neutralizing HIV-1 antibodies. PLoS Pathogens |
| title | Diverse pathways of escape from all well-characterized VRC01-class broadly neutralizing HIV-1 antibodies. |
| title_full | Diverse pathways of escape from all well-characterized VRC01-class broadly neutralizing HIV-1 antibodies. |
| title_fullStr | Diverse pathways of escape from all well-characterized VRC01-class broadly neutralizing HIV-1 antibodies. |
| title_full_unstemmed | Diverse pathways of escape from all well-characterized VRC01-class broadly neutralizing HIV-1 antibodies. |
| title_short | Diverse pathways of escape from all well-characterized VRC01-class broadly neutralizing HIV-1 antibodies. |
| title_sort | diverse pathways of escape from all well characterized vrc01 class broadly neutralizing hiv 1 antibodies |
| url | http://europepmc.org/articles/PMC6117093?pdf=render |
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