Abstract
Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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AIDS Vaccines / immunology*
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Amino Acid Sequence
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Animals
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Antibodies, Neutralizing / chemistry
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Antibodies, Neutralizing / genetics
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Antibodies, Neutralizing / immunology
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Antibodies, Neutralizing / ultrastructure
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Antibody Affinity
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Antibody Specificity / immunology
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Antigen-Antibody Complex / immunology
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B-Lymphocytes / cytology
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B-Lymphocytes / immunology*
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Cell Proliferation
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Clone Cells / cytology
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Clone Cells / immunology*
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Cloning, Molecular
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Cross-Priming / immunology
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Cryoelectron Microscopy
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Female
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HIV Antibodies / chemistry
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HIV Antibodies / genetics
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HIV Antibodies / immunology
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HIV Antibodies / ultrastructure
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HIV-1 / chemistry*
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HIV-1 / immunology*
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Immunodominant Epitopes / chemistry
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Immunodominant Epitopes / immunology
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Immunodominant Epitopes / ultrastructure
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Lymphocyte Activation
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Macaca mulatta / immunology*
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Male
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Mice
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Models, Molecular
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Polysaccharides / immunology
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Rabbits
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Somatic Hypermutation, Immunoglobulin
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Vaccination*
Substances
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AIDS Vaccines
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Antibodies, Neutralizing
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Antigen-Antibody Complex
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HIV Antibodies
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Immunodominant Epitopes
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Polysaccharides