Genetic Passive Immunization with Adenoviral Vector Expressing Chimeric Nanobody-Fc Molecules as Therapy for Genital Infection Caused by Mycoplasma hominis.

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 consid...

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Main Authors: Daria A Burmistrova, Sergey V Tillib, Dmitry V Shcheblyakov, Inna V Dolzhikova, Dmitry N Shcherbinin, Olga V Zubkova, Tatiana I Ivanova, Amir I Tukhvatulin, Maxim M Shmarov, Denis Y Logunov, Boris S Naroditsky, Aleksandr L Gintsburg
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4786110?pdf=render
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author Daria A Burmistrova
Sergey V Tillib
Dmitry V Shcheblyakov
Inna V Dolzhikova
Dmitry N Shcherbinin
Olga V Zubkova
Tatiana I Ivanova
Amir I Tukhvatulin
Maxim M Shmarov
Denis Y Logunov
Boris S Naroditsky
Aleksandr L Gintsburg
author_facet Daria A Burmistrova
Sergey V Tillib
Dmitry V Shcheblyakov
Inna V Dolzhikova
Dmitry N Shcherbinin
Olga V Zubkova
Tatiana I Ivanova
Amir I Tukhvatulin
Maxim M Shmarov
Denis Y Logunov
Boris S Naroditsky
Aleksandr L Gintsburg
author_sort Daria A Burmistrova
collection DOAJ
description 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.
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spelling doaj.art-164c15adc31444e6ab091391e560d24e2022-12-21T20:48:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01113e015095810.1371/journal.pone.0150958Genetic Passive Immunization with Adenoviral Vector Expressing Chimeric Nanobody-Fc Molecules as Therapy for Genital Infection Caused by Mycoplasma hominis.Daria A BurmistrovaSergey V TillibDmitry V ShcheblyakovInna V DolzhikovaDmitry N ShcherbininOlga V ZubkovaTatiana I IvanovaAmir I TukhvatulinMaxim M ShmarovDenis Y LogunovBoris S NaroditskyAleksandr L GintsburgDeveloping 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.http://europepmc.org/articles/PMC4786110?pdf=render
spellingShingle Daria A Burmistrova
Sergey V Tillib
Dmitry V Shcheblyakov
Inna V Dolzhikova
Dmitry N Shcherbinin
Olga V Zubkova
Tatiana I Ivanova
Amir I Tukhvatulin
Maxim M Shmarov
Denis Y Logunov
Boris S Naroditsky
Aleksandr L Gintsburg
Genetic Passive Immunization with Adenoviral Vector Expressing Chimeric Nanobody-Fc Molecules as Therapy for Genital Infection Caused by Mycoplasma hominis.
PLoS ONE
title Genetic Passive Immunization with Adenoviral Vector Expressing Chimeric Nanobody-Fc Molecules as Therapy for Genital Infection Caused by Mycoplasma hominis.
title_full Genetic Passive Immunization with Adenoviral Vector Expressing Chimeric Nanobody-Fc Molecules as Therapy for Genital Infection Caused by Mycoplasma hominis.
title_fullStr Genetic Passive Immunization with Adenoviral Vector Expressing Chimeric Nanobody-Fc Molecules as Therapy for Genital Infection Caused by Mycoplasma hominis.
title_full_unstemmed Genetic Passive Immunization with Adenoviral Vector Expressing Chimeric Nanobody-Fc Molecules as Therapy for Genital Infection Caused by Mycoplasma hominis.
title_short Genetic Passive Immunization with Adenoviral Vector Expressing Chimeric Nanobody-Fc Molecules as Therapy for Genital Infection Caused by Mycoplasma hominis.
title_sort genetic passive immunization with adenoviral vector expressing chimeric nanobody fc molecules as therapy for genital infection caused by mycoplasma hominis
url http://europepmc.org/articles/PMC4786110?pdf=render
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