Author:
Williams Wilton B.,Alam S. Munir,Ofek Gilad,Erdmann Nathaniel,Montefiori David,Seaman Michael S.,Wagh Kshitij,Korber Bette,Edwards Robert J.,Mansouri Katayoun,Eaton Amanda,Cain Derek W.,Martin Mitchell,Parks Robert,Barr Maggie,Foulger Andrew,Anasti Kara,Patel Parth,Sammour Salam,Parsons Ruth J.,Huang Xiao,Lindenberger Jared,Fetics Susan,Janowska Katarzyna,Niyongabo Aurelie,Janus Benjamin M.,Astavans Anagh,Fox Christopher B.,Mohanty Ipsita,Evangelous Tyler,Chen Yue,Berry Madison,Kirshner Helene,Van Itallie Elizabeth,Saunders Kevin,Wiehe Kevin,Cohen Kristen W.,McElrath M. Juliana,Corey Lawrence,Acharya Priyamvada,Walsh Stephen R.,Baden Lindsey R.,Haynes Barton F.
Abstract
SummaryA critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV-1, bnAbs take years to develop. The HVTN 133 clinical trial studied a peptide/liposome immunogen targeting B cell lineages of HIV-1 envelope membrane proximal external region (MPER) bnAbs (NCT03934541). Here, we report MPER peptide-liposome induction of polyclonal HIV-1 B cell lineages of mature bnAbs and their precursors, the most potent of which neutralized 15% of global tier 2 HIV-1 strains and 35% of clade B strains, with lineage initiation after the second immunization. Neutralization was enhanced by vaccine-selection of improbable mutations that increased antibody binding to gp41 and lipids. This study demonstrates proof-of-concept for rapid vaccine induction of human B cell lineages with heterologous neutralizing activity and selection of antibody improbable mutations, and outlines a path for successful HIV-1 vaccine development.
Publisher
Cold Spring Harbor Laboratory
Cited by
3 articles.
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