Chlamydial polymorphic membrane proteins: regulation, function and potential vaccine candidates

Vasilevsky, Sam; Stojanov, Miloš; Greub, Gilbert; Baud, David

doi:10.1080/21505594.2015.1111509

Cited by 66 publications

(86 citation statements)

References 108 publications

(140 reference statements)

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“…In C. trachomatis and C. muridarum , previously called C. trachomatis mouse pneumonitis, there are nine pmp genes [26]. Chlamydial Pmps form a group of proteins that have multiple repeats of conserved GGA (I,L,V) and FxxN tetrapeptide motifs in their N-terminus and central regions with MWs ranging from ~100–150 kDa [25, 27–31]. Pmps have three functional domains including a cleavable sec -dependent N-terminal signal for translocation through the cytoplasmic membrane, a C-terminal β-barrel sequence for outer membrane translocation, and a passenger domain for secretion or cell surface localization.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the nine polymorphic membrane proteins of Chlamydia trachomatis for their ability to induce protective immune responses in mice against a C. muridarum challenge

Pal

Favaroni

Tifrea

et al. 2017

Vaccine

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Objectives To test vaccines, formulated with novel antigens, to protect mice against Chlamydia infections. Methods To determine the ability of polymorphic membrane proteins (Pmps) to induce cross-species protective immune responses, recombinant fragments from all nine C. trachomatis serovar E Pmps were used to vaccinate BALB/c mice utilizing CpG-1826 and Montanide ISA 720 as adjuvants. C. muridarum recombinant MOMP and PBS, formulated with the same adjuvants, were used as positive and negative controls, respectively. Mice were challenged intranasally with 104 inclusion-forming units (IFU) of C. muridarum. Animals were weighed daily and at 10 days post-challenge, they were euthanized, their lungs harvested, weighed and the number of chlamydial IFU counted. Results Following vaccination the nine Pmps elicited immune responses. Based on body weight changes, or number of IFU recovered from lungs, mice vaccinated with Pmp C, G or H were the best protected. For example, over the 10-day period, the negative control group vaccinated with PBS lost significantly more body weight than mice immunized with PmpC or G (P < 0.05). C. muridarum MOMP vaccinated mice were better protected against body weight losses than any group immunized with Pmps. Also, the median number of IFU recovered from the lungs of mice vaccinated with PmpC (72 x 106) or PmpH (61 x 106) was significantly less than from mice immunized with PBS (620 x 106; P < 0.05). As determined by the number of IFU, all Pmps elicited less protection than C. muridarum MOMP (0.078 x 106 IFU; P < 0.05). Conclusions This is the first time PmpC has been shown to elicit cross-protection against a respiratory challenge. Additional work with Pmps C, G and H is recommended to determine their ability to protect animal models against genital and ocular challenges. Keywords: C. trachomatis, polymorphic membrane proteins (Pmps), vaccine, C. muridarum, PmpC,

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Section: Introductionmentioning

confidence: 99%

Comparison of the nine polymorphic membrane proteins of Chlamydia trachomatis for their ability to induce protective immune responses in mice against a C. muridarum challenge

Pal

Favaroni

Tifrea

et al. 2017

Vaccine

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“…As in the case of McAbs of other specificity, the required characteristic of the panel of antibodies obtained was their epitopic specificity. At the same time, analyzing the data of various authors regarding the structure and localization of MOMP in the cytoplasmic membrane, the features of the human humoral immune response to this protein (Wang et al, 2006;Vasilevsky et al, 2016), as well as the results of their own research on the competition of some McAbs with polyclonal sera of patients with urogenital chlamydiosis, it was decided to use the method of epitope mapping based on the technology of phage display (the establishment of directly amino acid residues with which antibodies interact). This study was conducted for the most affinity antibodies that competed (McAbs 291F8 and 293F4) and did not compete (McAb 296G2) with the polyclonal antibodies of the serum at the sites of antigen binding.…”

Section: Discussionmentioning

confidence: 99%

Biotechnology for obtaining hybrid positive control samples for immunoassay for detecting antibodies against Chlamydia trachomatis

Galkin

Gorshunov

Besarab

et al. 2018

Regul. Mech. Biosyst.

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The enzyme-linked immunosorbent assay (ELISA) is the most informative and versatile method of serological diagnostics. The possibility of detection by ELISA of specific antibodies of different classes allow one to differentiate primary infectious processes and their remission, exacerbation and chronic disease (holding of differential diagnosis). This approach is implemented in the methodology for evaluation of patients for the presence of humoral immune response against TORCH-infections pathogens (toxoplasmosis, rubella, cytomegalovirus, herpes simplex viruses infections, and some others). Therefore, testing for the presence of specific IgG and IgM antibodies against TORCH-infection pathogens in blood serum is an important element of mother and child protection. The essential problem in the production of IgM-capture ELISA diagnostic kits is obtaining positive control. The classic version of positive control is human blood serum (plasma) containing specific antibodies. But specific IgM-positive sera are insignificant raw material. This fact can significantly limit the production of diagnostic kits, especially in case of large-scale manufacture. We have suggested a methodological approach to the use of synthetic positive controls in IgM-capture ELISA kits based on conjugate of normal human IgM and monoclonal antibodies against horseradish peroxidase. It was found that it is possible to realize such a task by means of NHS ester-maleimide-mediated conjugation (by sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate), reductive amination-mediated conjugation (by sodium periodate) and glutaraldehyde-mediated conjugation. It was found that conjugates of normal human IgM and monoclonal antibodies against horseradish peroxidase obtained using NHS ester-mediated maleimide conjugation and periodate method are homogeneous in molecular weight, whereas conjugate synthesized by glutaraldehyde method comprises at least three types of biopolymers with close molecular weight. It was found that synthetic positive control obtained by different methods are characterized by higher titre compared to IgM-positive high-titre serum. However, positive control obtained by NHS ester-mediated maleimide conjugation has the best titration profile characteristics. We have suggested a methodological approach to the use of synthetic positive controls in indirect ELISA kits based on conjugate of normal human IgM (IgA) and monoclonal antibodies against major outer membrane protein of Ch. trachomatis. It was found that it is possible to realize such task by means of NHS ester-maleimide-mediated conjugation (by sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate) and reductive amination-mediated conjugation (by sodium periodate). It was found that synthetic positive control obtained by different methods are characterized by higher titre compared to IgM- and IgA-positive high-titre serum. However, positive control obtained by NHS ester-mediated maleimide conjugation has the best titration profile characteristics, both at the release time and after a week’s storage at 37 °C.

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“…The Polymorphic Membrane Protein family (Pmp A-I) are promising vaccine candidates for C. trachomatis because they are immunodominant and located on the outer membrane of the bacterium [19] . These proteins function as autotransporters involved in the delivery of virulence factors [20] . PmpD in particular is an interesting candidate because it is highly conserved, showing 99.1% amino acid identity among C. trachomatis serovars [21] .…”

Section: Spotlight On Original Articlesmentioning

confidence: 99%

Saliva biomarkers in neurological disorders: A “spitting image” of brain health?

Walton¹

2018

Biomedical Journal

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Chlamydial polymorphic membrane proteins: regulation, function and potential vaccine candidates

Cited by 66 publications

References 108 publications

Comparison of the nine polymorphic membrane proteins of Chlamydia trachomatis for their ability to induce protective immune responses in mice against a C. muridarum challenge

Comparison of the nine polymorphic membrane proteins of Chlamydia trachomatis for their ability to induce protective immune responses in mice against a C. muridarum challenge

Biotechnology for obtaining hybrid positive control samples for immunoassay for detecting antibodies against Chlamydia trachomatis

Saliva biomarkers in neurological disorders: A “spitting image” of brain health?

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