Structure-guided changes at the V2 apex of HIV-1 clade C trimer enhance elicitation of autologous neutralizing and broad V1V2-scaffold antibodies
HIV-1 clade C envelope immunogens that elicit both neutralizing and non-neutralizing V1V2-scaffold-specific antibodies (protective correlates from RV144 human trial) are urgently needed due to the prevalence of this clade in the most impacted regions worldwide. To achieve this, we introduce structur...
| Main Authors: | , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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Elsevier BV
2023
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| Online Access: | https://hdl.handle.net/1721.1/147834 |
| _version_ | 1826192351919341568 |
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| author | Sahoo, Anusmita Hodge, Edgar A LaBranche, Celia C Styles, Tiffany M Shen, Xiaoying Cheedarla, Narayanaiah Shiferaw, Ayalnesh Ozorowski, Gabriel Lee, Wen-Hsin Ward, Andrew B Tomaras, Georgia D Montefiori, David C Irvine, Darrell J Lee, Kelly K Amara, Rama Rao |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Sahoo, Anusmita Hodge, Edgar A LaBranche, Celia C Styles, Tiffany M Shen, Xiaoying Cheedarla, Narayanaiah Shiferaw, Ayalnesh Ozorowski, Gabriel Lee, Wen-Hsin Ward, Andrew B Tomaras, Georgia D Montefiori, David C Irvine, Darrell J Lee, Kelly K Amara, Rama Rao |
| author_sort | Sahoo, Anusmita |
| collection | MIT |
| description | HIV-1 clade C envelope immunogens that elicit both neutralizing and non-neutralizing V1V2-scaffold-specific antibodies (protective correlates from RV144 human trial) are urgently needed due to the prevalence of this clade in the most impacted regions worldwide. To achieve this, we introduce structure-guided changes followed by consensus-C-sequence-guided optimizations at the V2 region to generate UFO-v2-RQH173 trimer. This improves the abundance of well-formed trimers. Following the immunization of rabbits, the wild-type protein fails to elicit any autologous neutralizing antibodies, but UFO-v2-RQH173 elicits both autologous neutralizing and broad V1V2-scaffold antibodies. The variant with a 173Y modification in the V2 region, most prevalent among HIV-1 sequences, shows decreased ability in displaying a native-like V1V2 epitope with time in vitro and elicited antibodies with lower neutralizing and higher V1V2-scaffold activities. Our results identify a stabilized clade C trimer capable of eliciting improved neutralizing and V1V2-scaffold antibodies and reveal the importance of the V2 region in tuning this. |
| first_indexed | 2024-09-23T09:10:28Z |
| format | Article |
| id | mit-1721.1/147834 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:10:28Z |
| publishDate | 2023 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1478342023-02-02T03:43:47Z Structure-guided changes at the V2 apex of HIV-1 clade C trimer enhance elicitation of autologous neutralizing and broad V1V2-scaffold antibodies Sahoo, Anusmita Hodge, Edgar A LaBranche, Celia C Styles, Tiffany M Shen, Xiaoying Cheedarla, Narayanaiah Shiferaw, Ayalnesh Ozorowski, Gabriel Lee, Wen-Hsin Ward, Andrew B Tomaras, Georgia D Montefiori, David C Irvine, Darrell J Lee, Kelly K Amara, Rama Rao Massachusetts Institute of Technology. Department of Biological Engineering HIV-1 clade C envelope immunogens that elicit both neutralizing and non-neutralizing V1V2-scaffold-specific antibodies (protective correlates from RV144 human trial) are urgently needed due to the prevalence of this clade in the most impacted regions worldwide. To achieve this, we introduce structure-guided changes followed by consensus-C-sequence-guided optimizations at the V2 region to generate UFO-v2-RQH173 trimer. This improves the abundance of well-formed trimers. Following the immunization of rabbits, the wild-type protein fails to elicit any autologous neutralizing antibodies, but UFO-v2-RQH173 elicits both autologous neutralizing and broad V1V2-scaffold antibodies. The variant with a 173Y modification in the V2 region, most prevalent among HIV-1 sequences, shows decreased ability in displaying a native-like V1V2 epitope with time in vitro and elicited antibodies with lower neutralizing and higher V1V2-scaffold activities. Our results identify a stabilized clade C trimer capable of eliciting improved neutralizing and V1V2-scaffold antibodies and reveal the importance of the V2 region in tuning this. 2023-02-01T17:33:57Z 2023-02-01T17:33:57Z 2022 2023-02-01T17:30:52Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147834 Sahoo, Anusmita, Hodge, Edgar A, LaBranche, Celia C, Styles, Tiffany M, Shen, Xiaoying et al. 2022. "Structure-guided changes at the V2 apex of HIV-1 clade C trimer enhance elicitation of autologous neutralizing and broad V1V2-scaffold antibodies." Cell Reports, 38 (9). en 10.1016/J.CELREP.2022.110436 Cell Reports Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | Sahoo, Anusmita Hodge, Edgar A LaBranche, Celia C Styles, Tiffany M Shen, Xiaoying Cheedarla, Narayanaiah Shiferaw, Ayalnesh Ozorowski, Gabriel Lee, Wen-Hsin Ward, Andrew B Tomaras, Georgia D Montefiori, David C Irvine, Darrell J Lee, Kelly K Amara, Rama Rao Structure-guided changes at the V2 apex of HIV-1 clade C trimer enhance elicitation of autologous neutralizing and broad V1V2-scaffold antibodies |
| title | Structure-guided changes at the V2 apex of HIV-1 clade C trimer enhance elicitation of autologous neutralizing and broad V1V2-scaffold antibodies |
| title_full | Structure-guided changes at the V2 apex of HIV-1 clade C trimer enhance elicitation of autologous neutralizing and broad V1V2-scaffold antibodies |
| title_fullStr | Structure-guided changes at the V2 apex of HIV-1 clade C trimer enhance elicitation of autologous neutralizing and broad V1V2-scaffold antibodies |
| title_full_unstemmed | Structure-guided changes at the V2 apex of HIV-1 clade C trimer enhance elicitation of autologous neutralizing and broad V1V2-scaffold antibodies |
| title_short | Structure-guided changes at the V2 apex of HIV-1 clade C trimer enhance elicitation of autologous neutralizing and broad V1V2-scaffold antibodies |
| title_sort | structure guided changes at the v2 apex of hiv 1 clade c trimer enhance elicitation of autologous neutralizing and broad v1v2 scaffold antibodies |
| url | https://hdl.handle.net/1721.1/147834 |
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