Abstract
We propose a rational approach to the generation of live viral vaccines: alteration of virally encoded type I IFN antagonists to attenuate virulence while retaining immunogenicity. We have explored this concept by using the influenza virus. Previously we have shown that the NS1 protein of influenza A virus possesses anti-IFN activity. We now present evidence that influenza A and B viruses encoding altered viral NS1 proteins are highly attenuated in the mouse host, yet provide protection from challenge with wild-type viruses.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Cell Line
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Chlorocebus aethiops
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DNA Primers
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Dogs
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Enzyme-Linked Immunosorbent Assay
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Female
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Influenza A virus / genetics*
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Influenza A virus / immunology
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Influenza B virus / genetics*
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Influenza B virus / immunology
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Influenza Vaccines / genetics*
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Influenza Vaccines / immunology
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Mice
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Mice, Inbred BALB C
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Mutagenesis, Site-Directed
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Vero Cells
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Viral Nonstructural Proteins / genetics*
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Viral Nonstructural Proteins / immunology
Substances
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DNA Primers
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INS1 protein, influenza virus
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Influenza Vaccines
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Viral Nonstructural Proteins