Disassembly of HIV envelope glycoprotein trimer immunogens is driven by antibodies elicited via immunization
Name
eabh2791.full.pdf
Description
Published version
Size
661.06 KB
Format
Adobe PDF
Checksum (MD5)
423cb25e367364912acafeeb672562cd
Author(s)
Turner, Hannah L.
Andrabi, Raiees
Cottrell, Christopher A.
Richey, Sara T.
Song, Ge
Callaghan, Sean
Anzanello, Fabio
Moyer, Tyson J.
Abraham, Wuhbet
Melo, Mariane Bandeira
Date Issued
July 2021
Journal
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Turner, Hannah L. et al. "Disassembly of HIV envelope glycoprotein trimer immunogens is driven by antibodies elicited via immunization." Science Advances 7, 31 (July 2021): eabh2791. © 2020 The Authors
Version
Final published version
Abstract
Rationally designed protein subunit vaccines are being developed for a variety of viruses including influenza, RSV, SARS-CoV-2, and HIV. These vaccines are based on stabilized versions of the primary targets of neutralizing antibodies on the viral surface, namely, viral fusion glycoproteins. While these immunogens display the epitopes of potent neutralizing antibodies, they also present epitopes recognized by non-neutralizing or weakly neutralizing (“off-target”) antibodies. Using our recently developed electron microscopy polyclonal epitope mapping approach, we have uncovered a phenomenon wherein off-target antibodies elicited by HIV trimer subunit vaccines cause the otherwise highly stabilized trimeric proteins to degrade into cognate protomers. Further, we show that these protomers expose an expanded suite of off-target epitopes, normally occluded inside the prefusion conformation of trimer, that subsequently elicit further off-target antibody responses. Our study provides critical insights for further improvement of HIV subunit trimer vaccines for future rounds of the iterative vaccine design process.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Terms of Use
Creative Commons Attribution NonCommercial License 4.0
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DOI of Published Version
https://doi.org/10.1126/sciadv.abh2791
