Genetic Passive Immunization with Adenoviral Vector Expressing Chimeric Nanobody-Fc Molecules as Therapy for Genital Infection Caused by Mycoplasma hominis
| Autor: | Aleksandr Leonidovich Gintsburg, Maxim M. Shmarov, Dmitry V. Shcheblyakov, Boris S. Naroditsky, A. I. Tukhvatulin, Daria A. Burmistrova, Dmitry N. Shcherbinin, Inna V. Dolzhikova, Sergey V. Tillib, Olga V. Zubkova, Denis Y. Logunov, Tatiana I. Ivanova |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Physiology Genetic enhancement Trichomonas Cell Membranes lcsh:Medicine Artificial Gene Amplification and Extension medicine.disease_cause Biochemistry Polymerase Chain Reaction Mice 0302 clinical medicine Mycoplasma Immune Physiology Medicine and Health Sciences Nanotechnology Public and Occupational Health Enzyme-Linked Immunoassays lcsh:Science Multidisciplinary Immune System Proteins Physics Gene Therapy Vaccination and Immunization Antibodies Bacterial Mycoplasma hominis Mice Inbred DBA 030220 oncology & carcinogenesis Physical Sciences Engineering and Technology Female Antibody Cellular Structures and Organelles Research Article Biotechnology Camelus Immunology Genetic Vectors Biophysics Passive Immunization Biology Research and Analysis Methods Antibodies Microbiology Viral vector Adenoviridae 03 medical and health sciences medicine Animals Mycoplasma Infections Immunoassays Molecular Biology Techniques Molecular Biology Clinical Genetics Bacteria lcsh:R Organisms Immunization Passive Biology and Life Sciences Proteins Membrane Proteins Pathogenic bacteria Cell Biology Single-Domain Antibodies biology.organism_classification Virology Immunoglobulin Fc Fragments 030104 developmental biology Bionanotechnology biology.protein Immunologic Techniques lcsh:Q Preventive Medicine |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 3, p e0150958 (2016) |
| ISSN: | 1932-6203 |
| Popis: | Developing pathogen-specific recombinant antibody fragments (especially nanobodies) is a very promising strategy for the treatment of infectious disease. Nanobodies have great potential for gene therapy application due to their single-gene nature. Historically, Mycoplasma hominis has not been considered pathogenic bacteria due to the lack of acute infection and partially due to multiple studies demonstrating high frequency of isolation of M. hominis samples from asymptomatic patients. However, recent studies on the role of latent M. hominis infection in oncologic transformation, especially prostate cancer, and reports that M. hominis infects Trichomonas and confers antibiotic resistance to Trichomonas, have generated new interest in this field. In the present study we have generated specific nanobody against M. hominis (aMh), for which the identified target is the ABC-transporter substrate-binding protein. aMh exhibits specific antibacterial action against M. hominis. In an attempt to improve the therapeutic properties, we have developed the adenoviral vector-based gene therapy approach for passive immunization with nanobodies against M. hominis. For better penetration into the mucous layer of the genital tract, we fused aMh with the Fc-fragment of IgG. Application of this comprehensive approach with a single systemic administration of recombinant adenovirus expressing aMh-Fc demonstrated both prophylactic and therapeutic effects in a mouse model of genital M. hominis infection. |
| Databáze: | OpenAIRE |
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