Abstract
Antibody-mediated immunotherapy is effective in humanized mice when combinations of broadly neutralizing antibodies (bNAbs) are used that target nonoverlapping sites on the human immunodeficiency virus type 1 (HIV-1) envelope. In contrast, single bNAbs can control simian-human immunodeficiency virus (SHIV) infection in immune-competent macaques, suggesting that the host immune response might also contribute to the control of viremia. Here, we investigate how the autologous antibody response in intact hosts can contribute to the success of immunotherapy. We find that frequently arising antibodies that normally fail to control HIV-1 infection can synergize with passively administered bNAbs by preventing the emergence of bNAb viral escape variants.
© 2014 Klein et al.
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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Animals
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Antibodies, Neutralizing / immunology*
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Antibodies, Neutralizing / therapeutic use
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Enzyme-Linked Immunosorbent Assay
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HEK293 Cells
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HIV Infections / immunology*
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HIV Infections / therapy
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HIV Infections / virology
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HIV-1 / genetics
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HIV-1 / immunology*
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HIV-1 / physiology
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Host-Pathogen Interactions / immunology
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Humans
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Immunotherapy / methods*
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Macaca mulatta
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Mice, Inbred NOD
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Mice, Knockout
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Mutation / immunology
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Simian Acquired Immunodeficiency Syndrome / immunology*
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Simian Acquired Immunodeficiency Syndrome / therapy
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Simian Acquired Immunodeficiency Syndrome / virology
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Simian Immunodeficiency Virus / genetics
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Simian Immunodeficiency Virus / immunology*
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Simian Immunodeficiency Virus / physiology
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Viral Envelope Proteins / immunology
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Viral Load / immunology
Substances
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Antibodies, Neutralizing
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Viral Envelope Proteins