Vaccine against chlamydia BD584

https://www.ncbi.nlm.nih.gov/pubmed/27325352

Vaccine.< 2016 Jul 25;34(34):3979-85. doi: 10.1016/j.vaccine.2016.06.046. Epub 2016 Jun 17.

Immunization with chlamydial type III secretion antigens reduces vaginal shedding and prevents fallopian tube pathology following live C. muridarum challenge.

Abstract

Chlamydia trachomatis infectionsi in women are often asymptomatic and if left untreated can lead to significant late sequelae including pelvic inflammatory disease and tubal factor infertility. Vaccine development efforts over the past three decades have been unproductive and there is no vaccine approved for use in humans. The existence of serologically distinct strains or serovars of C. trachomatis mandates a vaccine that will provide protection against multiple serovars. Chlamydia spp. use a highly conserved type III secretion system (T3SS) composed of both structural and effector proteins which is an essential virulence factor for infection and intracellulari replication. In this study we evaluated a novel fusion protein antigen (BD584) which consists of three T3SS proteins from C. trachomatis (CopB, CopD, and CT584) as a potential chlamydial vaccine candidate. Intranasal immunization with BD584 elicited serum neutralizing antibodies that inhibited C. trachomatis infection in vitro. Following intravaginal challenge with C. muridarum, immunized mice had a 95% reduction in chlamydial shedding from the vagina at the peak of infection and cleared the infection sooner than control mice. Immunization with BD584 also reduced the rate of hydrosalpinx by 87.5% compared to control mice. Together, these results suggest that highly conserved proteins of the chlamydial T3SS may represent good candidates for a Chlamydia vaccine.

Copyright © 2016 Elsevier Ltd. All rights reserved.

James B. Mahony

BSc, PhD
Professor

Research Interests

Dr. Mahony’s research interests focus on the pathophysiology of respiratory pathogens including influenza, SARS and coronaviruses and the obligate intracellulari bacterial pathogen Chlamydia pneumoniae.

One of the major focuses of the laboratory is the development of new antimicrobial agents for both respiratory viruses and chlamydiae. Most antimicrobial agents are small molecules and interact with a small number of amino acids of the target protein. The laboratory is developing peptide mimetics that will target protein-protein interactive domains (20-30 aa) that should be refractory to the development of resistance. We have developed a novel influenza inhibitor that blocks viral transcription and are presently testing it against high pathogenicity avian influenza virus. The second major research interest of the laboratory is the characterization of proteins of the type III secretion system of Chlamydia and elucidating how these proteins interact to form the secretion apparatus. The goal is to identify novel drug targets and then develop peptidomimetics that will inhibit protein interaction and type III secretion. We have recently been successful with this approach and have developed inhibitors for type III secretion in C. pneumoniae, C. trachomatis, and Pseudomonas aeruginosa (a major respiratory pathogen) that inhibit bacterial cell invasion.

Additional projects in the laboratory include the elucidation of how coronaviruses interfere with the innate immunei response in myeloid dendritic cellsi, identification of host cell proteins controlling West Nile virus infection, and development of improved diagnostic tests for potentially pandemic influenza viruses.

Contact

McMaster University
St. Joseph's Healthcare

telephone: 905-521-6021
email: mahonyj@mcmaster.ca<

Program Area

Infection & Immunity

Research Focus

Emerging viral infectionsi, Chlamydia vaccine development, Anti-viral therapeutics, Genetic engineering of commensal bacteria to deliver therapeutic proteins

Selected Publications

  • Chlamydia pneumoniae CopD translocator protein plays a critical role in type III secretion (T3S) and infection. Bulir DC, Waltho DA, Stone CB, Mwawasi KA, Nelson JC, Mahony JB.

    PLoS One. 2014 Jun 24;9(6):e99315. doi: 10.1371/journal.pone.0099315. eCollection 2014.

  • Structural characterization of a novel Chlamydia pneumoniae type III secretion-associated protein, Cpn0803. Stone CB, Sugiman-Marangos S, Bulir DC, Clayden RC, Leighton TL, Slootstra JW, Junop MSi, Mahony JB. PLoS One. 2012;7(1):e30220. doi: 10.1371/journal.pone.0030220. Epub 2012 Jan 17.
  • Molecular diagnosis of respiratory virus infections. Mahony JB, Petrich A, Smieja M.

    Crit Rev Clin Lab Sci. 2011 Sep-Dec;48(5-6):217-49. doi: 10.3109/10408363.2011.640976. Review.

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