Abstract
Vaccine-induced protection against infection by HIV or highly pathogenic and virulent SIV strains has been limited. In a proof-of-concept study, we show that a novel vaccine approach significantly protects rhesus macaques from mucosal infection by the highly pathogenic strain SIVmac251. We vaccinated three cohorts of 12 macaques each with live, irradiated vaccine cells secreting the modified endoplasmic reticulum chaperone gp96-Ig. Cohort 1 was vaccinated with cells secreting gp96(SIV)Ig carrying SIV peptides. In addition, Cohort 2 received recombinant envelope protein SIV-gp120. Cohort 3 was injected with cells secreting gp96-Ig (no SIV Ags) vaccines. Cohort 2 was protected from infection. After seven rectal challenges with highly pathogenic SIVmac251, the hazard ratio was 0.27, corresponding to a highly significant, 73% reduced risk for viral acquisition. The apparent success of the novel vaccine modality recommends further study.
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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Adjuvants, Immunologic / administration & dosage
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Animals
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Antibodies, Viral / biosynthesis
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Cohort Studies
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Female
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HEK293 Cells
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Humans
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Injections, Intraperitoneal
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Intestinal Mucosa / immunology*
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Intestinal Mucosa / pathology
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Intestinal Mucosa / virology
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Macaca mulatta
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Male
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Membrane Glycoproteins / administration & dosage*
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Membrane Glycoproteins / therapeutic use*
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Mucous Membrane / immunology
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Mucous Membrane / virology
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Rectal Diseases / immunology
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Rectal Diseases / prevention & control
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Rectal Diseases / virology
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SAIDS Vaccines / administration & dosage*
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SAIDS Vaccines / immunology
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Simian Acquired Immunodeficiency Syndrome / immunology*
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Simian Acquired Immunodeficiency Syndrome / pathology
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Simian Acquired Immunodeficiency Syndrome / prevention & control*
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Simian Immunodeficiency Virus / immunology*
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Simian Immunodeficiency Virus / pathogenicity
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / pathology
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T-Lymphocytes, Cytotoxic / virology
Substances
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Adjuvants, Immunologic
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Antibodies, Viral
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Membrane Glycoproteins
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SAIDS Vaccines
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endoplasmin