Toll-Like Receptor 2-Dependent Activity of Native Major Outer Membrane Protein Proteosomes of Chlamydia trachomatis

Massi, Paola; Toussi, Deana N.; Tifrea, Delia F.; Maza, Luis M. de la

doi:10.1128/iai.01062-12

Cited by 40 publications

(33 citation statements)

References 56 publications

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“…This effect has been described to be TLR2-dependent. Recent work has shown that nMOMP-Ps induce TLR2-dependent cell activation in vitro , similar to the porins mentioned above [24]. The observed induction of immune responses as well as protective effect of nMOMP-Ps in mice immunized in the absence of additional adjuvants may be explained, at least in part, by such TLR2-dependent cell responses.…”

Section: Discussionmentioning

confidence: 58%

“…Purified nMOMP, identified by electrophoresis on 10% tricine SDS-PAGE and Western blot using the monoclonal antibody MoPn-40 to MOMP, was precipitated by centrifugation following the addition of 80% (v/v) ethanol and incubation overnight at −20°C. The protein was resuspended in 10 mM HEPES, pH 7.2, with 10% D-octylglucoside (DOG; Anatrace), followed by extensive dialysis in PBS containing 0.02% NaN 3 for formation of detergent-free protein micelles (proteosomes) [24]. …”

Section: Methodsmentioning

confidence: 99%

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Vaccination with major outer membrane protein proteosomes elicits protection in mice against a Chlamydia respiratory challenge

Tifrea

Pal

Toussi

et al. 2013

Microbes and Infection

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Vaccines formulated with the Chlamydia muridarum native major outer membrane protein (nMOMP) have so far been shown to elicit the most robust protection against this pathogen. nMOMP is a membrane protein and therefore, detergents are used to keep it in solution. Detergents however, have toxic effects. To address this limitation, we tested a nMOMP proteosome vaccine and compared it for its ability to elicit protection against nMOMP solubilized in the detergent Z3-14. The two preparations were formulated with or without CpG + Montanide (C/M). As a control antigen we used ovalbumin. Mice vaccinated with nMOMP developed strong humoral and cell mediated Chlamydia-specific immune responses. Based on the IgG2a/IgG1 levels in serum and amounts of IFN-γ in splenocytes supernatants the immune responses were predominantly Th1-biased. The animals were subsequently challenged intranasally with 2×103 Chlamydia inclusion forming units (IFU) and the course of the infection was followed for 10 days when the mice were euthanized. Based on changes in body weight, weight of the lungs and number of IFU recovered from the lungs, mice immunized with nMOMP-Ps and nMOMP+Z3-14 adjuvanted with C/M showed the most robust protection. In summary, nMOMP-Ps should be considered as Chlamydia vaccine candidates.

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Section: Discussionmentioning

confidence: 58%

Section: Methodsmentioning

confidence: 99%

Vaccination with major outer membrane protein proteosomes elicits protection in mice against a Chlamydia respiratory challenge

Tifrea

Pal

Toussi

et al. 2013

Microbes and Infection

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“…In the present study, the reduction in MOMP and TLR2 expression in infected macrophages exposed to encapsulated-M278 serum are indicative of less Chlamydia infectivity of macrophages. Conversely, as TLR2, a cognate C. trachomatis receptor is critical for Chlamydia -mediated host cell-activation and MOMP signaling 49 ; the presence of more Chlamydia in macrophages would correlate with higher TLR2 and MOMP expressions as observed in macrophages exposed to bare M278 or control sera. The low level of CD80 expression, that is critical for T cell-activation, also agrees with results obtained in CD80/CD86 knockout mice, which are resistant to a primary C. trachomatis infection 50 .…”

Section: Discussionmentioning

confidence: 99%

Poly(lactic acid)–poly(ethylene glycol) nanoparticles provide sustained delivery of a Chlamydia trachomatis recombinant MOMP peptide and potentiate systemic adaptive immune responses in mice

Dixit

Singh

Yilma

et al. 2014

Nanomedicine: Nanotechnology, Biology and Medicine

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PLA-PEG [poly (lactic acid)-poly (ethylene glycol)], a biodegradable copolymer, is underexploited for vaccine delivery although it exhibits enhanced biocompatibility and slow release immune-potentiating properties. We document here successful encapsulation of M278, a Chlamydia trachomatis MOMP (major outer membrane protein) peptide, within PLA-PEG nanoparticles by size (~73–100 nm), zeta potential (−16 mV), smooth morphology, encapsulation efficiency (~60%), slow release pattern, and non-toxicity to macrophages. Immunization of mice with encapsulated-M278 elicited higher M278-specific T-cell cytokines [Th1 (IFN-γ, IL-2), Th17 (IL-17)] and antibodies [Th1 (IgG2a), Th2 (IgG1, IgG2b)] compared to bare M278. Encapsulated-M278 mouse serum inhibited Chlamydia infectivity of macrophages, with a concomitant transcriptional down-regulation of MOMP, its cognate TLR2 and CD80 co-stimulatory molecule. Collectively, encapsulated-M278 potentiated crucial adaptive immune responses, which are required by a vaccine candidate for protective immunity against Chlamydia. Our data highlights PLA-PEG’s potential for vaccines, which resides in its slow release and potentiating effects to bolster immune responses.

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“…3 However, both TLR2 and TLR4 deficient mice were able to clear the infection similarly to wild-type mice. Both human and mouse data [4][5][6] indicate that TLR2 is the primary pathogen-recognition receptor in the upper genital tract able to alert the immune system and to drive the immune-pathogenic mechanisms associated with chlamydia infection. A chlamydia subunit vaccine adjuvanted with a TLR4 agonist may reduce or eliminate immunopathogenesis associated with C. trachomatis signaling through TLR2.…”

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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Toll-Like Receptor 2-Dependent Activity of Native Major Outer Membrane Protein Proteosomes of Chlamydia trachomatis

Cited by 40 publications

References 56 publications

Vaccination with major outer membrane protein proteosomes elicits protection in mice against a Chlamydia respiratory challenge

Vaccination with major outer membrane protein proteosomes elicits protection in mice against a Chlamydia respiratory challenge

Poly(lactic acid)–poly(ethylene glycol) nanoparticles provide sustained delivery of a Chlamydia trachomatis recombinant MOMP peptide and potentiate systemic adaptive immune responses in mice

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

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