National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
UM1AI100663
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
UM1AI144462
米国
Bill & Melinda Gates Foundation
OPP1115782
米国
Bill & Melinda Gates Foundation
INV-002916
米国
引用
ジャーナル: bioRxiv / 年: 2021 タイトル: Disassembly of HIV envelope glycoprotein trimer immunogens is driven by antibodies elicited via immunization. 著者: 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 ...著者: 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 / 要旨: 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.