Abstract
Intestinal and free-living protozoa, such as Giardia lamblia, express a dense coat of variant-specific surface proteins (VSPs) on trophozoites that protects the parasite inside the host's intestine. Here we show that VSPs not only are resistant to proteolytic digestion and extreme pH and temperatures but also stimulate host innate immune responses in a TLR-4 dependent manner. We show that these properties can be exploited to both protect and adjuvant vaccine antigens for oral administration. Chimeric Virus-like Particles (VLPs) decorated with VSPs and expressing model surface antigens, such as influenza virus hemagglutinin (HA) and neuraminidase (NA), are protected from degradation and activate antigen presenting cells in vitro. Orally administered VSP-pseudotyped VLPs, but not plain VLPs, generate robust immune responses that protect mice from influenza infection and HA-expressing tumors. This versatile vaccine platform has the attributes to meet the ultimate challenge of generating safe, stable and efficient oral vaccines.
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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Administration, Oral
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Animals
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Antigen Presentation / drug effects
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Bioengineering / methods
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Dendritic Cells / virology
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Female
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Gene Expression
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Giardia lamblia / chemistry*
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Hemagglutinin Glycoproteins, Influenza Virus / genetics
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Hemagglutinin Glycoproteins, Influenza Virus / immunology
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Humans
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Immunity, Innate / drug effects
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Influenza Vaccines / administration & dosage
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Influenza Vaccines / genetics
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Influenza Vaccines / immunology*
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Male
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Membrane Proteins / genetics
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Membrane Proteins / immunology*
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Mice
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Mice, Transgenic
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Neuraminidase / genetics
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Neuraminidase / immunology
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Orthomyxoviridae Infections / immunology
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Orthomyxoviridae Infections / prevention & control*
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Orthomyxoviridae Infections / virology
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Protein Stability
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Protozoan Proteins / genetics
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Protozoan Proteins / immunology*
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Toll-Like Receptor 4 / genetics
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Toll-Like Receptor 4 / immunology
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Trophozoites / chemistry
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Vaccination
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Vaccines, Virus-Like Particle / administration & dosage
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Vaccines, Virus-Like Particle / genetics
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Vaccines, Virus-Like Particle / immunology*
Substances
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Adjuvants, Immunologic
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Hemagglutinin Glycoproteins, Influenza Virus
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Influenza Vaccines
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Membrane Proteins
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Protozoan Proteins
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Tlr4 protein, mouse
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Toll-Like Receptor 4
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Vaccines, Virus-Like Particle
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hemagglutinin, human influenza A virus
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Neuraminidase