title: Genetic Passive Immunization with Adenoviral Vector Expressing Chimeric Nanobody-Fc Molecules as Therapy for Genital Infection Caused by Mycoplasma hominis.
abstract: 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.
authors.affiliation: Department of Immunobiotechnology, Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia.
authors.forename: Daria A
authors.initials: DA
authors.lastname: Burmistrova
authors.affiliation: Department of Molecular Biotechnology, Institute of Gene Biology, Moscow, Russia.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Tillib
authors.affiliation: Department of Immunobiotechnology, Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia.
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Shcheblyakov
authors.affiliation: Department of Cellular Microbiology, Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia.
authors.forename: Inna V
authors.initials: IV
authors.lastname: Dolzhikova
authors.affiliation: Department of Molecular Biotechnology, Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia.
authors.forename: Dmitry N
authors.initials: DN
authors.lastname: Shcherbinin
authors.affiliation: Department of Molecular Biotechnology, Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Zubkova
authors.affiliation: Department of Molecular Biotechnology, Institute of Gene Biology, Moscow, Russia.
authors.forename: Tatiana I
authors.initials: TI
authors.lastname: Ivanova
authors.affiliation: Department of Cellular Microbiology, Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia.
authors.forename: Amir I
authors.initials: AI
authors.lastname: Tukhvatulin
authors.affiliation: Department of Molecular Biotechnology, Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia.
authors.forename: Maxim M
authors.initials: MM
authors.lastname: Shmarov
authors.affiliation: Department of Cellular Microbiology, Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia.
authors.forename: Denis Y
authors.initials: DY
authors.lastname: Logunov
authors.affiliation: Department of Immunobiotechnology, Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia.
authors.forename: Boris S
authors.initials: BS
authors.lastname: Naroditsky
authors.affiliation: Director of Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia.
authors.forename: Aleksandr L
authors.initials: AL
authors.lastname: Gintsburg
mesh_terms: D000256:Adenoviridae; D000818:Animals; D000907:Antibodies, Bacterial / Q000235:genetics / Q000276:immunology*; D002162:Camelus / Q000235:genetics / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D007116:Immunization, Passive; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009175:Mycoplasma Infections / Q000276:immunology* / Q000517:prevention & control; D019535:Mycoplasma hominis / Q000276:immunology*; D061905:Single-Domain Antibodies / Q000235:genetics / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D007141:Immunoglobulin Fc Fragments; D061905:Single-Domain Antibodies