Abstract
Current efforts to develop Zika virus (ZIKV) subunit vaccines have been focused on pre-membrane (prM) and envelope (E) proteins, but the role of NS1 in ZIKV-specific immune response and protection is poorly understood. Here, we develop an attenuated recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing ZIKV prM-E-NS1 as a polyprotein. This vectored vaccine candidate is attenuated in mice, where a single immunization induces ZIKV-specific antibody and T cell immune responses that provide protection against ZIKV challenge. Co-expression of prM, E, and NS1 induces significantly higher levels of Th2 and Th17 cytokine responses than prM-E. In addition, NS1 alone is capable of conferring partial protection against ZIKV infection in mice even though it does not induce neutralizing antibodies. These results demonstrate that attenuated rVSV co-expressing prM, E, and NS1 is a promising vaccine candidate for protection against ZIKV infection and highlights an important role for NS1 in ZIKV-specific cellular immune responses.
Publication types
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Research Support, N.I.H., Extramural
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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, Viral / immunology
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Antigens, Viral / genetics
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Antigens, Viral / immunology
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Antigens, Viral / metabolism
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Cytokines / metabolism
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Disease Models, Animal
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Female
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Genetic Vectors / immunology
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Male
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Mice
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Mice, Inbred BALB C
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Polyproteins / genetics
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Polyproteins / immunology*
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Th17 Cells / metabolism
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Th2 Cells / metabolism
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Vaccination
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Vaccines, Attenuated
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Vaccines, DNA / immunology
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Vaccines, Synthetic
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Vesiculovirus / immunology
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Viral Envelope Proteins / genetics
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Viral Envelope Proteins / immunology
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Viral Nonstructural Proteins / genetics
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Viral Nonstructural Proteins / immunology*
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Viral Nonstructural Proteins / metabolism*
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Viral Vaccines / genetics
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Viral Vaccines / immunology*
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Zika Virus / genetics
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Zika Virus / immunology
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Zika Virus / metabolism*
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Zika Virus Infection / immunology
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Zika Virus Infection / prevention & control*
Substances
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Antibodies, Neutralizing
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Antibodies, Viral
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Antigens, Viral
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Cytokines
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NS1 protein, zika virus
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Polyproteins
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Vaccines, Attenuated
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Vaccines, DNA
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Vaccines, Synthetic
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Viral Envelope Proteins
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Viral Nonstructural Proteins
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Viral Vaccines
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prM protein, Flavivirus