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Evaluation of the Immunogenic Potential of Membrane Vesicles from Clinical Isolates of Gardnerella vaginalis in a Murine Model of Bacterial Vaginosis

Implementing Organization

Icmr- National Institute For Research In Reproductive And Child Health
Principal Investigator
Dr. Vikrant Madhukar Bhor
Icmr- National Institute For Research In Reproductive And Child Health, Maharashtra
bhorv@nirrh.res.in
CO-Principal Investigator
Nil

Project Overview

Bacterial vaginosis (BV) is a common, genital tract condition afflicting women in the reproductive age group. It associated not only with development of adverse obstetric and gynaecological complications but also with increased susceptibility to acquisition of STIs including HIV. Clinical management of BV is largely limited to antibiotic therapy. Although antibiotic therapies are efficient, they are insufficient in keeping BV at bay resulting in recurrences and asymptomatic incidences of BV. Precise molecular mechanisms employed by G. vaginalis for initiation and progression of BV as well as those linked to recurrence of BV have not been delineated. Since G. vaginalis is also found in healthy women and there is substantial genotypic and phenotypic diversity, it is not known if certain critical components such as virulence factors are exclusively present only in BV associated strains leading to triggering of infection and pathogenesis. but it is also associated with issues such as development of antibiotic resistance which may lead to recurrence and relapse. Therefore, there is a need to explore novel approaches such as modulation of immune responses for effective control of BV. Membrane vesicles (MVs), nanosized, lipid membrane containing structures secreted by bacteria are widely recognized to possess immunogenic potential on account of their diverse antigenic cargo. Existing literature demonstrates the utility of MVs in modulation of immune responses in case of several infections followed by clearance of the infection in experimental animal models. Such approaches have not been explored in the context of BV. In view of this we propose to evaluate the immunogenic potential of MVs obtained from clinical isolates of G. vaginalis in a murine model of BV. The objectives of the project are (1) To isolate G. vaginalis strains from healthy women and women with bacterial vaginosis (BV) and to perform biochemical and molecular characterization of the isolates (2) To isolate and perform biochemical and biophysical characterization of membrane vesicles (MVs) from clinical isolates of G. vaginalis and in vitro investigation of their cytotoxic and inflammatory action on vaginal epithelial cells (3)To examine the immunogenic potential of MVs from clinical isolates of G. vaginalis in a mouse model of BV. Membrane vesicles (MVs) obtained from these clinical isolates will be subjected to biochemical and biophysical characterization as well as proteomic analysis and examination of their effect on cytotoxicity and inflammatory responses in vaginal epithelial cells. In the event that MVs of G. vaginalis clinical isolates exhibit superior or comparable immunogenic potential to infection by G. vaginalis cell in the experimental mouse model of BV and subsequently if immunisation with these MVs result in early clearance of G. vaginalis infection challenge, then the MVs will be investigated further as potential clinical applications.
Funding Organization
Quick Information
Area of Research
Life Sciences & Biotechnology
Focus Area
Biomedical And Health Sciences (Bhs)
Start Date
13 Jun 2024
End Date
12 Jun 2027
Status
ongoing
Output
No. of Research Paper
00
Technologies (If Any)
00
No. of PhD Produced
00
Publications
00
No. of Patents
Filed : 00
Grant : 00
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