Abstract
The viral strain responsible for smallpox infection is variola major (VARV). As a result of the successful eradication of smallpox with the vaccinia virus (VACV), the general population is no longer required to receive a smallpox vaccine, and will have no protection against smallpox. This lack of immunity is a concern due to the potential for use of smallpox as a biological weapon. Considerable progress has been made in the development of subunit-based smallpox vaccines resulting from the identification of VACV protective antigens. It also offers the possibility of using antigens from VARV to formulate the next generation subunit-based smallpox vaccines. Here, we show that codon-optimized DNA vaccines expressing three VARV antigens (A30, B7 and F8) and their recombinant protein counterparts elicited high-titer, cross-reactive, VACV neutralizing antibody responses in mice. Vaccinated mice were protected from intraperitoneal and intranasal challenges with VACV. These results suggest the feasibility of a subunit smallpox vaccine based on VARV antigen sequences to induce immunity against poxvirus infection.
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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Amino Acid Sequence
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Animals
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Antigens, Viral / genetics
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Antigens, Viral / immunology
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Body Weight
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Cell Line
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Chemoprevention / methods
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Enzyme-Linked Immunosorbent Assay
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Escherichia coli / genetics
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Feasibility Studies
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Female
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Humans
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Immunization Schedule
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Immunoglobulin G / blood
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Immunoglobulin G / immunology
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Kidney / cytology
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Mice
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Mice, Inbred BALB C
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Models, Animal
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Molecular Sequence Data
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Neutralization Tests
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Sequence Homology, Amino Acid
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Smallpox / immunology
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Smallpox / prevention & control*
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Smallpox Vaccine / administration & dosage
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Smallpox Vaccine / genetics
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Smallpox Vaccine / immunology*
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Vaccines, Attenuated / administration & dosage
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Vaccines, Attenuated / genetics
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Vaccines, Attenuated / immunology*
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Vaccines, DNA / genetics
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Vaccines, DNA / immunology
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Vaccines, Subunit / immunology
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Vaccinia virus / immunology*
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Variola virus / genetics
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Variola virus / immunology
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Variola virus / pathogenicity
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Viral Vaccines*
Substances
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Antigens, Viral
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Immunoglobulin G
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Smallpox Vaccine
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Vaccines, Attenuated
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Vaccines, DNA
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Vaccines, Subunit
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Viral Vaccines