Development status and future prospects for a vaccine against Chlamydia trachomatis infection

Hafner, Louise M.; Wilson, David; Timms, Peter

doi:10.1016/j.vaccine.2013.08.020

Cited by 80 publications

(61 citation statements)

References 119 publications

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“…Although there is currently no vaccine available against C. trachomatis, prophylactic vaccination could have a dramatic impact on the health of sexually active people. 2 Studies in mice have shown that pathogenesis resulting from a chlamydia infection on the oviduct and mesosalpinx is dependent on signaling through Toll-like receptor 2 (TLR2) and not TLR4. 3 However, both TLR2 and TLR4 deficient mice were able to clear the infection similarly to wild-type mice.…”

Section: Introductionmentioning

confidence: 99%

Phosphate substitution in an AlOOH - TLR4 adjuvant system (SPA08) modulates the immunogenicity of Serovar E MOMP from Chlamydia trachomatis

Visan

Sanchez

Kania

et al. 2016

Human Vaccines & Immunotherapeutics

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Chlamydia trachomatis is one of the most common sexually transmitted pathogens and the development of an effective vaccine is highly desirable. The Major Outer Membrane Protein (MOMP) is one of the most abundant and immunogenic chlamydial proteins. Here we investigated the effects of phosphate substitution on the physicochemical and immunochemical properties of an experimental vaccine composed of serovar E recombinant MOMP (rMOMP) and a proprietary adjuvant system SPA08, consisting of aluminum oxyhydroxide (AlOOH) containing the TLR4 agonist E6020.An increase in phosphate substitution in the AlOOH component of the adjuvant markedly decreased the adsorptive coefficient and adsorptive capacity for both Ser E rMOMP and E6020. In vaccine formulations used for immunizations, phosphate substitution induced a decrease in the % adsorption of Ser E rMOMP without affecting the % adsorption of E6020.Immunogenicity studies in CD1 mice showed that an increase in phosphate substitution of the SPA08 adjuvant resulted in an increase in Ser E rMOMP-specific serum total IgG and IgG1 but not IgG2a titers. The degree of phosphate substitution in SPA08 also significantly increased in vitro neutralization concomitant with a decrease in proinflammatory cytokines secreted by Ser E rMOMP-restimulated splenocytes.Taken together, the results of these studies suggest that the degree of phosphate substitution in AlOOH greatly affects the adsorption of E6020 and Ser E rMOMP to AlOOH resulting in significant effects on vaccine-induced cellular and humoral responses.

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Section: Introductionmentioning

confidence: 99%

Phosphate substitution in an AlOOH - TLR4 adjuvant system (SPA08) modulates the immunogenicity of Serovar E MOMP from Chlamydia trachomatis

Visan

Sanchez

Kania

et al. 2016

Human Vaccines & Immunotherapeutics

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“…But to improve the insight into designing an effective vaccine, it is crucial to get concrete knowledge about immunological aspect of this infection, besides the role of both humoral and cellular immunity as two arms of immune system. Indeed, successful protection requires the stimulation of T-cell in addition to antibody responses [21]. In the current study, we were being able to predict precisely antigenic region through bioinformatic and antigenicity prediction tools to produce a truncated protein instead of a full-length.…”

Section: Discussionmentioning

confidence: 91%

Cloning and Expression of Truncated Chlamydial Major Outer Membrane Protein in E.coli: A Miniature Step Forward

Bitazar¹,

Farivar²,

Hajikhani³

et al. 2014

J Vaccines Vaccin

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Administration of Prophylactic vaccines still is the cutting-edge of prevention, control and elimination of infections. Among the common causes of sexually transmitted diseases, chlamydia trachomatis is an important socioeconomic burden worldwide which impairs human genital tract function, resulting in severe complications like urethritis, pelvic inflammatory disease (PID), getting ease of HIV transmission, playing cofactor role in human papilloma virus (HPV)-induced cervical neoplasia, and unfortunately infertility. Because of all difficulties, vaccination is considered to be the most economical and reliable way to escape from unrestrained exacerbation states of infection than any other prevalence program. But despite much advancement in the field of veterinary, the dream has yet to be realized. Among a number of potential candidates, the major outer membrane protein (MOMP) is a vanguard of subunit vaccines. In this attempt, MOMP217 gene fragment cloned in PET28b+ and expressed in E.coli. The protein expression confirmed by SDS-PAGE. These findings demonstrate that, considering the antigenicity prediction and due to the existence of potential epitopic region, rMOMP217 could be a potential capable peptide which can represent as an alternative to whole MOMP. Journal of Vaccines & Vaccination Cloning of PET-MOMP217PCR was performed to amplify the MOMP217 containing epitopic regions with specific primers. Qiagen gel extraction kit (Qiagen, Hilden, Germany) was used to purify PCR amplified product and plasmid DNA. Purified plasmid and amplified insert were double digested with BamHI and HindIII (Fermentase). The digested products were purified and ligated into linearised and purified vector withT4 DNA ligase enzyme(Fermentase), then ligation mixture were transformed into E.coli DH5α cloning host. As well, Recombinant clones were confirmed by colony PCR and double digestion. The confirmed purified DH5α/ pET-MOMP217 positive colony were transformed and cloned into E.coli BL21 (DE3) expression host and used for protein expression purpose with IPTG. Protein expressionE.coli BL2 (DE3) with T7 promoter, harboring the PET-MOMP217 (24kDa) positive colony were grown in 100 ml LB broth at 37°C including 100 µg/ml kanamycin (Sigma) to achieve an optical density (OD) of 0.7 (stationary growth phase) at 600 nm at this time, 1 mM isopropyl-ß-D-thiogalactoside (IPTG; Invitrogen) were added to 50 ml LB broth and the other same amount were considered as uninduced (-IPTG) control. Incubation was continued at 37°C. The samples from induced and uninduced culture were collected within 2, 4, 6 hours and overnight after induction. Incubation temperature in the case of overnight was reduced to 25°C. Samples were accumulated, centrifuged at 6000 rpm for 5 min. Harvested cells were resuspending with 2x loading protein buffer containing 2-ME, boiled and subjected to SDS-PAGE analysis. Total protein expression trend were evaluated by 10% SDS-PAGE stained with Comassie Brilliant Blue. SDS-PAGE were shown to have one band corresponded t...

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“…Not surprisingly, surface-exposed membrane proteins such as the MOMP, Omp2, and several Pmps, including PmpD and PmpG, are a major focus. 130 However, a wide range of intracellular proteins (NrdB, HtrA, GroEL, Nqr3, MAC-perforin, DnaK, IncA) as well as secreted proteins (Tarp, CPAF, CopB) are also showing promise. [131][132][133][134][135] The strategies for identifying key antigens is also improving.…”

Section: The Choice Of Immunogenic Target Antigens Is Rapidly Expandingmentioning

confidence: 99%

Development of a vaccine for Chlamydia trachomatis: challenges and current progress

Hafner¹

2015

VDT

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Abstract:Chlamydia trachomatis remains an enigmatic bacterial pathogen with no vaccine yet available to treat human ocular and genital tract infections caused by tissue-tropic serovars of the organism. Globally, it is the leading cause of preventable blindness as well as the leading cause of bacterial sexually transmitted infections. The pathogen has a range of virulence factors that enable it to successfully evade both the innate and adaptive immune system of the host. The host immune system, although protective, paradoxically is also associated closely with the pathologies of trachoma and pelvic inflammatory disease -disease sequelae of some chlamydial infections and reinfections in some genetically susceptible hosts. In this review, we focus on what is known currently about the pathogenesis of ocular and genital infections caused by this mucosal pathogen. We also discuss novel insights into the pathogenesis of infections caused by the genital and ocular serovars of C. trachomatis, including a discussion of both pathogen and host factors, such as the human microbiota at these mucosal sites as well as the current immunological challenges facing vaccine development. Finally, we discuss the current progress toward development of a vaccine against C. trachomatis. A wide range of recombinant protein antigens are being identified and, hence, are available for vaccine trials. A plasmid-free live strain has recently been produced and evaluated in the mouse (Chlamydia muridarum) and monkey (C. trachomatis) models. The data for ocular infections in the monkey model was particularly encouraging, although the path to regulatory approval of a live vaccine is still uncertain. While still a major challenge, vaccines for ocular and genital C. trachomatis infections are looking more promising.

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Development status and future prospects for a vaccine against Chlamydia trachomatis infection

Cited by 80 publications

References 119 publications

Phosphate substitution in an AlOOH - TLR4 adjuvant system (SPA08) modulates the immunogenicity of Serovar E MOMP from Chlamydia trachomatis

Phosphate substitution in an AlOOH - TLR4 adjuvant system (SPA08) modulates the immunogenicity of Serovar E MOMP from Chlamydia trachomatis

Cloning and Expression of Truncated Chlamydial Major Outer Membrane Protein in E.coli: A Miniature Step Forward

Development of a vaccine for Chlamydia trachomatis: challenges and current progress

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