Protection Against<i>Chlamydia trachomatis</i>Infection and Upper Genital Tract Pathological Changes by Vaccine-Promoted Neutralizing Antibodies Directed to the VD4 of the Major Outer Membrane Protein

Olsen, Anja; Follmann, Frank; Erneholm, Karin; Rosenkrands, Ida; Andersen, Peter

doi:10.1093/infdis/jiv137

Cited by 108 publications

(174 citation statements)

References 49 publications

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“…For example, passive transfer of immune serum protects mice against Chlamydia genital infection only in the presence of CD4 + T cells [55]. Several studies have linked antibodies to protection against upper genital pathology [60–63]. Antibodies of IgG2a isotype mediate effector functions, including antibody-dependent cell-mediated cytotoxicity (ADCC), with evidence suggesting that this effector function facilitates early clearance of chlamydial infections.…”

Section: Discussionmentioning

confidence: 99%

Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity againstChlamydia muridarumIntravaginal Infection

Koroleva

Kobets

Щербинин

et al. 2017

BioMed Research International

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Chlamydia trachomatis imposes serious health problems and causes infertility. Because of asymptomatic onset, it often escapes antibiotic treatment. Therefore, vaccines offer a better option for the prevention of unwanted inflammatory sequelae. The existence of serologically distinct serovars of C. trachomatis suggests that a vaccine will need to provide protection against multiple serovars. Chlamydia spp. use a highly conserved type III secretion system (T3SS) composed of structural and effector proteins which is an essential virulence factor. In this study, we expressed the T3SS needle protein of Chlamydia muridarum, TC_0037, an ortholog of C. trachomatis CdsF, in a replication-defective adenoviral vector (AdTC_0037) and evaluated its protective efficacy in an intravaginal Chlamydia muridarum model. For better immune responses, we employed a heterologous prime-boost immunization protocol in which mice were intranasally primed with AdTC_0037 and subcutaneously boosted with recombinant TC_0037 and Toll-like receptor 4 agonist monophosphoryl lipid A mixed in a squalene nanoscale emulsion. We found that immunization with TC_0037 antigen induced specific humoral and T cell responses, decreased Chlamydia loads in the genital tract, and abrogated pathology of upper genital organs. Together, our results suggest that TC_0037, a highly conserved chlamydial T3SS protein, is a good candidate for inclusion in a Chlamydia vaccine.

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Section: Discussionmentioning

confidence: 99%

Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity againstChlamydia muridarumIntravaginal Infection

Koroleva

Kobets

Щербинин

et al. 2017

BioMed Research International

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“…Cells were seeded in six-well plates at 5 × 10 5 cells per well and the monolayers were infected by centrifugation after 24 h with C. trachomatis serovar D/UW-3/CX at a multiplicity of infection of 4 (15). Infected cells were incubated in the absence or presence of IFN-γ (2 ng/ml equaling 40 IU/ml).…”

Section: Methodsmentioning

confidence: 99%

Quantitative Protein Profiling of Chlamydia trachomatis Growth Forms Reveals Defense Strategies Against Tryptophan Starvation

Østergaard

Follmann

Olsen

et al. 2016

Molecular & Cellular Proteomics

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Chlamydia trachomatis is one of the most common sexually transmitted bacterial pathogens in humans. The infection is often asymptomatic and can lead to chronic manifestations. The infectious elementary body and the replicating reticulate body are the two growth forms in the normal developmental cycle. Under the influence of interferon-γ, the normal cycle is disrupted because of tryptophan degradation, leading to a third persistent form, the aberrant reticulate body.For the genital strain C. trachomatis D/UW-3/CX we established a quantitative, label-free proteomic approach, and identified in total 655 out of 903 (73%) predicted proteins, allowing the first quantitative comparison of all three growth forms. Inclusion membrane proteins and proteins involved in translation were more abundant in the reticulate body (RB)1 and aberrant reticulate body (ARB) forms, whereas proteins of the type III Secretion System and the cell envelope were more abundant in the elementary body (EB) form, reflecting the need for these proteins to establish infection and for host interactions.In the interferon-γ induced ARB proteome, the tryptophan synthase subunits were identified as biomarkers with a strong increase from less than 0.05% to 9% of the total protein content, reflecting an inherent defense strategy for the pathogen to escape interferon-γ mediated immune pressure. Furthermore, the total tryptophan content in the ARB form was 1.9-fold lower compared with the EB form, and we demonstrate that modulation of the protein repertoire toward lower abundance of proteins with high tryptophan content, is a mechanism which contributes to establish and maintain chlamydial persistence. Thus, quantitative proteomics provides insights in the Chlamydia defense mechanisms to escape interferon-γ mediated immune pressure.

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“…MOMP is a highly abundant surface antigen that has long been considered a promising candidate. Novel formulations delivering this protein via cationic liposomes induced antibody, type-1 immunity and partial protection from infection in minipigs 184 and significant protection against upper tract disease in mice 185186. Intranasal immunization using MOMP in combination with Nanostat ™ , oil-in-water nanoemulsion in mice after challenge 187.…”

Section: Treatment and Preventionmentioning

confidence: 99%

Chlamydia trachomatis Genital Infections

O’Connell¹,

Ferone²

2016

MIC

174

153

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Etiology, transmission and protection: Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infection (STI) globally. However, C. trachomatis also causes trachoma in endemic areas, mostly Africa and the Middle East, and is a leading cause of preventable blindness worldwide. Epidemiology, incidence and prevalence: The World Health Organization estimates 131 million new cases of C. trachomatis genital infection occur annually. Globally, infection is most prevalent in young women and men (14-25 years), likely driven by asymptomatic infection, inadequate partner treatment and delayed development of protective immunity. Pathology/Symptomatology: C. trachomatis infects susceptible squamocolumnar or transitional epithelial cells, leading to cervicitis in women and urethritis in men. Symptoms are often mild or absent but ascending infection in some women may lead to Pelvic Inflammatory Disease (PID), resulting in reproductive sequelae such as ectopic pregnancy, infertility and chronic pelvic pain. Complications of infection in men include epididymitis and reactive arthritis. Molecular mechanisms of infection: Chlamydiae manipulate an array of host processes to support their obligate intracellular developmental cycle. This leads to activation of signaling pathways resulting in disproportionate influx of innate cells and the release of tissue damaging proteins and pro-inflammatory cytokines. Treatment and curability: Uncomplicated urogenital infection is treated with azithromycin (1 g, single dose) or doxycycline (100 mg twice daily x 7 days). However, antimicrobial treatment does not ameliorate established disease. Drug resistance is rare but treatment failures have been described. Development of an effective vaccine that protects against upper tract disease or that limits transmission remains an important goal.

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Protection AgainstChlamydia trachomatisInfection and Upper Genital Tract Pathological Changes by Vaccine-Promoted Neutralizing Antibodies Directed to the VD4 of the Major Outer Membrane Protein

Cited by 108 publications

References 49 publications

Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity againstChlamydia muridarumIntravaginal Infection

Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity againstChlamydia muridarumIntravaginal Infection

Quantitative Protein Profiling of Chlamydia trachomatis Growth Forms Reveals Defense Strategies Against Tryptophan Starvation

Chlamydia trachomatis Genital Infections

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