Structure-guided changes at the V2 apex of HIV-1 clade C trimer enhance elicitation of autologous neutralizing and broad V1V2-scaffold antibodies
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1-s2.0-S2211124722001632-main.pdf
Description
Published version
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4.01 MB
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Author(s)
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
Date Issued
2022
Journal
Cell Reports
Publisher
Elsevier BV
Citation
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).
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CELREP.2022.110436
