National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
UM1AI100663
United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
UM1AI144462
United States
Bill & Melinda Gates Foundation
OPP1115782
United States
Bill & Melinda Gates Foundation
INV-002916
United States
Citation
Journal: bioRxiv / Year: 2021 Title: Disassembly of HIV envelope glycoprotein trimer immunogens is driven by antibodies elicited via immunization. Authors: Hannah L Turner / Raiees Andrabi / Christopher A Cottrell / Sara T Richey / Ge Song / Sean Callaghan / Fabio Anzanello / Tyson J Moyer / Wuhbet Abraham / Mariane Melo / Murillo Silva / ...Authors: Hannah L Turner / Raiees Andrabi / Christopher A Cottrell / Sara T Richey / Ge Song / Sean Callaghan / Fabio Anzanello / Tyson J Moyer / Wuhbet Abraham / Mariane Melo / Murillo Silva / Nicole Scaringi / Eva G Rakasz / Quentin Sattentau / Darrell J Irvine / Dennis R Burton / Andrew B Ward / 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 ...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 or weakly neutralizing ("off-target") antibodies. Using our recently developed electron microscopy 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.
History
Deposition
Jan 26, 2021
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Header (metadata) release
Jun 23, 2021
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Map release
Jun 23, 2021
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Update
Jun 23, 2021
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Current status
Jun 23, 2021
Processing site: RCSB / Status: Released
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