Effects of partially dismantling the CD4 binding site glycan fence of HIV-1 envelope glycoprotein trimers on neutralizing antibody induction
Previously, VLPs bearing JR-FL strain HIV-1 Envelope trimers elicited potent neutralizing antibodies (nAbs) in 2/8 rabbits PLoS Pathog 11(5): e1004932) by taking advantage of a naturally absent glycan at position 197 that borders the CD4 binding site (CD4bs). In new immunizations, we attempted to im...
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| Format: | Article |
| Language: | English |
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Elsevier
2017
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| Online Access: | http://eprints.sunway.edu.my/479/ http://eprints.sunway.edu.my/479/1/Tommy%20Tong.pdf |
| _version_ | 1848801829080530944 |
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| author | Crooks, Ema T Osawa, Keiko Tong, Tommy Yuh Koon * Grimley, Samantha L Dai, Yang D Whalen, Robert G Kulp, Daniel W Menis, Sergey Schief, William R Binley, James M |
| author_facet | Crooks, Ema T Osawa, Keiko Tong, Tommy Yuh Koon * Grimley, Samantha L Dai, Yang D Whalen, Robert G Kulp, Daniel W Menis, Sergey Schief, William R Binley, James M |
| author_sort | Crooks, Ema T |
| building | SU Institutional Repository |
| collection | Online Access |
| description | Previously, VLPs bearing JR-FL strain HIV-1 Envelope trimers elicited potent neutralizing antibodies (nAbs) in 2/8 rabbits PLoS Pathog 11(5): e1004932) by taking advantage of a naturally absent glycan at position 197 that borders the CD4 binding site (CD4bs). In new immunizations, we attempted to improve nAb responses by removing the N362 glycan that also lines the CD4bs. All 4 rabbits developed nAbs. One targeted the N197 glycan hole like our previous sera. Two sera depended on the N463 glycan, again suggesting CD4bs overlap. Heterologous boosts appeared to reduce nAb clashes with the N362 glycan. The fourth serum targeted a N362 glycan-sensitive epitope. VLP manufacture challenges prevented us from immunizing larger rabbit numbers to empower a robust statistical analysis. Nevertheless, trends suggest that targeted glycan removal may improve nAb induction by exposing new epitopes and that it may be possible to modify nAb speciUcity using rational heterologous boosts. |
| first_indexed | 2025-11-14T21:13:40Z |
| format | Article |
| id | sunway-479 |
| institution | Sunway University |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T21:13:40Z |
| publishDate | 2017 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | sunway-4792020-01-23T03:28:53Z http://eprints.sunway.edu.my/479/ Effects of partially dismantling the CD4 binding site glycan fence of HIV-1 envelope glycoprotein trimers on neutralizing antibody induction Crooks, Ema T Osawa, Keiko Tong, Tommy Yuh Koon * Grimley, Samantha L Dai, Yang D Whalen, Robert G Kulp, Daniel W Menis, Sergey Schief, William R Binley, James M Q Science (General) QR355 Virology Previously, VLPs bearing JR-FL strain HIV-1 Envelope trimers elicited potent neutralizing antibodies (nAbs) in 2/8 rabbits PLoS Pathog 11(5): e1004932) by taking advantage of a naturally absent glycan at position 197 that borders the CD4 binding site (CD4bs). In new immunizations, we attempted to improve nAb responses by removing the N362 glycan that also lines the CD4bs. All 4 rabbits developed nAbs. One targeted the N197 glycan hole like our previous sera. Two sera depended on the N463 glycan, again suggesting CD4bs overlap. Heterologous boosts appeared to reduce nAb clashes with the N362 glycan. The fourth serum targeted a N362 glycan-sensitive epitope. VLP manufacture challenges prevented us from immunizing larger rabbit numbers to empower a robust statistical analysis. Nevertheless, trends suggest that targeted glycan removal may improve nAb induction by exposing new epitopes and that it may be possible to modify nAb speciUcity using rational heterologous boosts. Elsevier 2017 Article PeerReviewed text en cc_by_nc_nd http://eprints.sunway.edu.my/479/1/Tommy%20Tong.pdf Crooks, Ema T and Osawa, Keiko and Tong, Tommy Yuh Koon * and Grimley, Samantha L and Dai, Yang D and Whalen, Robert G and Kulp, Daniel W and Menis, Sergey and Schief, William R and Binley, James M (2017) Effects of partially dismantling the CD4 binding site glycan fence of HIV-1 envelope glycoprotein trimers on neutralizing antibody induction. Virology, 505. pp. 193-209. ISSN 0042 6822 (In Press) http://dx.doi.org/10.1016/j.virol.2017.02.024 |
| spellingShingle | Q Science (General) QR355 Virology Crooks, Ema T Osawa, Keiko Tong, Tommy Yuh Koon * Grimley, Samantha L Dai, Yang D Whalen, Robert G Kulp, Daniel W Menis, Sergey Schief, William R Binley, James M Effects of partially dismantling the CD4 binding site glycan fence of HIV-1 envelope glycoprotein trimers on neutralizing antibody induction |
| title | Effects of partially dismantling the CD4 binding site glycan fence of HIV-1 envelope glycoprotein trimers on neutralizing antibody induction |
| title_full | Effects of partially dismantling the CD4 binding site glycan fence of HIV-1 envelope glycoprotein trimers on neutralizing antibody induction |
| title_fullStr | Effects of partially dismantling the CD4 binding site glycan fence of HIV-1 envelope glycoprotein trimers on neutralizing antibody induction |
| title_full_unstemmed | Effects of partially dismantling the CD4 binding site glycan fence of HIV-1 envelope glycoprotein trimers on neutralizing antibody induction |
| title_short | Effects of partially dismantling the CD4 binding site glycan fence of HIV-1 envelope glycoprotein trimers on neutralizing antibody induction |
| title_sort | effects of partially dismantling the cd4 binding site glycan fence of hiv-1 envelope glycoprotein trimers on neutralizing antibody induction |
| topic | Q Science (General) QR355 Virology |
| url | http://eprints.sunway.edu.my/479/ http://eprints.sunway.edu.my/479/ http://eprints.sunway.edu.my/479/1/Tommy%20Tong.pdf |