Abstract
Using an Escherichia coli-grown plasmid vector encoding a fragment of thioredoxin (Trx) fused to a central region (amino acids 128 to 229) of the respiratory syncytial virus (RSV) (Long strain) G protein, we employed site-directed mutagenesis to investigate the importance of selected amino acids to vaccine efficacy. Mice were immunized with a total of 10 wild-type or mutant Trx-G proteins and challenged intranasally with RSV. Striking differences in the induction of RSV G-protein-specific antibodies, protection against RSV challenge, cytokine RNA responses, and induction of RSV-associated eosinophilic inflammation were observed among the mutant proteins examined. Taken together, the results identify a critical role for specific amino acids in the induction of protective immunity and priming for eosinophilia against RSV.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic
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Alum Compounds
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Animals
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Antibodies, Viral / blood
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Cytokines / genetics
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Cytokines / metabolism*
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Eosinophilia*
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Lung / immunology
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Mice
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Mutagenesis, Site-Directed
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Mutation
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Respiratory Syncytial Virus Infections / immunology*
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Respiratory Syncytial Virus Infections / prevention & control
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Respiratory Syncytial Virus Vaccines / genetics
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Respiratory Syncytial Virus Vaccines / immunology*
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Respiratory Syncytial Viruses / immunology*
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Vaccines, Synthetic / genetics
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Vaccines, Synthetic / immunology
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Viral Proteins / genetics*
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Viral Proteins / immunology*
Substances
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Adjuvants, Immunologic
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Alum Compounds
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Antibodies, Viral
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Cytokines
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RNA, Messenger
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Respiratory Syncytial Virus Vaccines
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Vaccines, Synthetic
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Viral Proteins
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aluminum sulfate