Immunogenicity of Outer Membrane Proteins VirB9-1 and VirB9-2, a Novel Nanovaccine against Anaplasma marginale

• Published in: PloS one Vol. 11; no. 4; p. e0154295
• Main Authors: Zhao, Liang, Mahony, Donna, Cavallaro, Antonino S, Zhang, Bing, Zhang, Jun, Deringer, James R, Zhao, Chun-Xia, Brown, Wendy C, Yu, Chengzhong, Mitter, Neena, Middelberg, Anton P J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 26-04-2016; Public Library of Science (PLoS)
• Subjects: Agriculture; Analysis; Anaplasma; Anaplasma marginale; Anaplasma marginale - drug effects; Anaplasma marginale - immunology; Anaplasmosis; Anaplasmosis - immunology; Anaplasmosis - microbiology; Anaplasmosis - prevention & control; Animal health; Animals; Antibodies, Bacterial - biosynthesis; Antigens; Antigens, Bacterial - administration & dosage; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Arachnids; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; B-Lymphocytes - pathology; Bacterial Outer Membrane Proteins - administration & dosage; Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - immunology; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - genetics; Bacterial Vaccines - immunology; Bioengineering; Biology and Life Sciences; Blood; Bovidae; Care and treatment; Cattle; Cattle Diseases - immunology; Cattle Diseases - microbiology; Cattle Diseases - prevention & control; Cell proliferation; Cell Proliferation - drug effects; Cell-mediated immunity; Cloning, Molecular; Drug Carriers - chemistry; Drug Carriers - metabolism; Drug delivery systems; E coli; Engineering and Technology; Escherichia coli; Escherichia coli - genetics; Escherichia coli - metabolism; Female; Formulations; Gene Expression; Health aspects; Humoral immunity; Immunity; Immunity, Cellular - drug effects; Immunity, Humoral - drug effects; Immunization; Immunogenicity; Immunology; Infections; Livestock; Lymphocyte Activation - drug effects; Lymphocytes B; Lymphocytes T; Medical research; Medicine and Health Sciences; Membrane proteins; Mice; Mice, Inbred C57BL; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Nanotechnology; Outer membrane proteins; Pore size; Porosity; Proteins; Quillaja saponaria; Recombinant Proteins - administration & dosage; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Research and Analysis Methods; Silica; Silicon dioxide; Silicon Dioxide - administration & dosage; Silicon Dioxide - chemistry; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - pathology; Type IV Secretion Systems - genetics; Type IV Secretion Systems - metabolism; Vaccines; Vesicles; Veterinary colleges; Veterinary medicine; Queensland Australia; Australia; United States > US; St Lucia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0154295

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.