Abstract
Anaplasma marginale is the most prevalent tick-borne livestock pathogen and poses a significant threat to cattle industry. In contrast to currently available live blood-derived vaccines against A. marginale, alternative safer and better-defined subunit vaccines will be of great significance. Two proteins (VirB9-1 and VirB9-2) from the Type IV secretion system of A. marginale have been shown to induce humoral and cellular immunity. In this study, Escherichia coli were used to express VirB9-1 and VirB9-2 proteins. Silica vesicles having a thin wall of 6 nm and pore size of 5.8 nm were used as the carrier and adjuvant to deliver these two antigens both as individual or mixed nano-formulations. High loading capacity was achieved for both proteins, and the mouse immunisation trial with individual as well as mixed nano-formulations showed high levels of antibody titres over 107 and strong T-cell responses. The mixed nano-formulation also stimulated high-level recall responses in bovine T-cell proliferation assays. These results open a promising path towards the development of efficient A. marginale vaccines and provide better understanding on the role of silica vesicles to deliver multivalent vaccines as mixed nano-formulations able to activate both B-cell and T-cell immunity, for improved animal health.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anaplasma marginale / drug effects*
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Anaplasma marginale / immunology
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Anaplasmosis / immunology
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Anaplasmosis / microbiology
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Anaplasmosis / prevention & control*
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Animals
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Antibodies, Bacterial / biosynthesis*
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Antigens, Bacterial / administration & dosage
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Antigens, Bacterial / genetics
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Antigens, Bacterial / immunology
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B-Lymphocytes / drug effects
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B-Lymphocytes / immunology
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B-Lymphocytes / pathology
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Bacterial Outer Membrane Proteins / administration & dosage
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Bacterial Outer Membrane Proteins / genetics
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Bacterial Outer Membrane Proteins / immunology*
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Bacterial Vaccines / administration & dosage
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Bacterial Vaccines / genetics
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Bacterial Vaccines / immunology
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Cattle
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Cattle Diseases / immunology
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Cattle Diseases / microbiology
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Cattle Diseases / prevention & control*
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Cell Proliferation / drug effects
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Cloning, Molecular
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Drug Carriers / chemistry
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Drug Carriers / metabolism
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Female
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Gene Expression
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Immunity, Cellular / drug effects*
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Immunity, Humoral / drug effects*
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Immunization
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Lymphocyte Activation / drug effects
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Mice
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Mice, Inbred C57BL
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Nanoparticles / chemistry
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Nanoparticles / ultrastructure
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / genetics
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Recombinant Proteins / immunology
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Silicon Dioxide / administration & dosage
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Silicon Dioxide / chemistry
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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T-Lymphocytes / pathology
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Type IV Secretion Systems / genetics
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Type IV Secretion Systems / metabolism
Substances
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Antibodies, Bacterial
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Antigens, Bacterial
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Bacterial Outer Membrane Proteins
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Bacterial Vaccines
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Drug Carriers
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Recombinant Proteins
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Type IV Secretion Systems
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Silicon Dioxide
Grants and funding
This work was supported by the Queensland Government Research Partnerships grant (Project 013936_471),
https://www.business.qld.gov.au/industry/science/grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.