scholarly journals Vaccination with the Recombinant Major Outer Membrane Protein Elicits Antibodies to the Constant Domains and Induces Cross-Serovar Protection against Intranasal Challenge with Chlamydia trachomatis

2013 ◽  
Vol 81 (5) ◽  
pp. 1741-1750 ◽  
Author(s):  
Delia F. Tifrea ◽  
Pooja Ralli-Jain ◽  
Sukumar Pal ◽  
Luis M. de la Maza
Keyword(s):  
Chlamydia Trachomatis ◽  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Median Number ◽  
Negative Control ◽  
Major Outer Membrane Protein ◽  
Control Groups ◽  
Content Type ◽  
Chlamydia Muridarum

ABSTRACTTo determine the ability of the major outer membrane protein (MOMP) to elicit cross-serovar protection, groups of mice were immunized by the intramuscular (i.m.) and subcutaneous (s.c.) routes with recombinant MOMP (rMOMP) fromChlamydia trachomatisserovars D (UW-3/Cx), E (Bour), or F (IC-Cal-3) orChlamydia muridarumstrain Nigg II using CpG-1826 and Montanide ISA 720 VG as adjuvants. Negative-control groups were immunized i.m. and s.c. withNeisseria gonorrhoeaerecombinant porin B (Ng-rPorB) or i.n. with Eagle's minimal essential medium (MEM-0). Following vaccination, the mice developed antibodies not only against the homologous serovar but also against heterologous serovars. The rMOMP-vaccinated animals also mounted cell-mediated immune responses as assessed by a lymphoproliferative assay. Four weeks after the last immunization, mice were challenged i.n. with 104inclusion-forming units (IFU) ofC. muridarum. The mice were weighed for 10 days and euthanized, and the number of IFU in their lungs was determined. At 10 days postinfection (p.i.), mice immunized with the rMOMP ofC. muridarumorC. trachomatisD, E, or F had lost 4%, 6%, 8%, and 8% of their initial body weight, respectively, significantly different from the negative-control groups (Ng-rPorB, 13%; MEM-0, 19%;P< 0.05). The median number of IFU recovered from the lungs of mice immunized withC. muridarumrMOMP was 0.13 × 106. The median number of IFU recovered from mice immunized with rMOMP from serovars D, E, and F were 0.38 × 106, 7.56 × 106, and 11.94 × 106IFU, respectively. All the rMOMP-immunized animals had significantly less IFU than theNg-rPorB (40 × 106)- or MEM-0 (70 × 106)-immunized mice (P< 0.05). In conclusion, vaccination with rMOMP can elicit protection against homologous and heterologousChlamydiaserovars.

scholarly journals Vaccination with the Chlamydia trachomatis Major Outer Membrane Protein Can Elicit an Immune Response as Protective as That Resulting from Inoculation with Live Bacteria

2005 ◽  
Vol 73 (12) ◽  
pp. 8153-8160 ◽  
Author(s):  
Sukumar Pal ◽  
Ellena M. Peterson ◽  
Luis M. de la Maza
Keyword(s):  
Immune Response ◽  
Chlamydia Trachomatis ◽  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Negative Control Group ◽  
Positive Control ◽  
Negative Control ◽  
Major Outer Membrane Protein ◽  
Control Group

ABSTRACT BALB/c mice were vaccinated by the intramuscular (i.m.) and subcutaneous (s.c.) routes with a native preparation of the Chlamydia trachomatis mouse pneumonitis (MoPn) major outer membrane protein (MOMP), using Montanide ISA 720 and CpG-1826 as adjuvants. A negative control group was immunized with ovalbumin and the two adjuvants, and a positive control group was immunized intranasally (i.n.) with 104 inclusion-forming units (IFU) of C. trachomatis. Four weeks after the last i.m.-plus-s.c. immunization, mice were challenged in the ovarian bursa with 105 IFU of C. trachomatis MoPn. Six weeks after the genital challenge, animals were mated, and the pregnancies were monitored. After vaccination with MOMP, the mice developed strong Chlamydia-specific humoral and cellular immune responses. Following the genital challenge, of the mice vaccinated with the MOMP, only 15% (3/20) had positive vaginal cultures, while 85% (17/20) of the animals immunized with ovalbumin had positive cultures over the 6 weeks of observation (P < 0.05). Also, only 14% (3/21) of the animals inoculated i.n. with Chlamydia had positive vaginal cultures. After mating, 75% (15/20) of the mice vaccinated with MOMP carried embryos in both uterine horns. Of the animals vaccinated i.n. with the Chlamydia, 81% (17/21) had embryos in both uterine horns (P > 0.05). In contrast, only 10% (2/20) of the mice immunized with ovalbumin had embryos in both uterine horns (P < 0.05). In conclusion, immunization with a purified preparation of the MOMP is as effective as vaccination with viable C. trachomatis in eliciting a protective immune response against a genital challenge in mice.

scholarly journals Vaccination with the recombinant major outer membrane protein elicits long-term protection in mice against vaginal shedding and infertility following a Chlamydia muridarum genital challenge

npj Vaccines ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Sukumar Pal ◽  
Maria I. Cruz-Fisher ◽  
Chunmei Cheng ◽  
Jennifer R. Carmichael ◽  
Delia F. Tifrea ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Neutralizing Antibodies ◽  
Positive Control ◽  
Negative Control ◽  
Major Outer Membrane Protein ◽  
Control Group ◽  
Chlamydia Muridarum

Abstract Implementation of a vaccine is likely the best approach to curtail Chlamydia trachomatis infections. The aim of this study was to determine the ability of a vaccine formulated with the recombinant major outer membrane protein (MOMP) and Th1 and Th2 adjuvants, delivered by combinations of systemic and mucosal routes, to elicit long-term protection in mice against a genital challenge with Chlamydia muridarum. As a negative control, mice were vaccinated with the recombinant Neisseria gonorrhoeae porinB, and the positive control group was immunized with C. muridarum live elementary bodies (EB). The four vaccines formulated with MOMP, as determined by the titers of IgG and neutralizing antibodies in serum, proliferative responses of T-cells stimulated with EB and levels of IFN-γ in the supernatants, elicited robust humoral and cellular immune responses over a 6-month period. Groups of mice were challenged genitally at 60, 120, or 180 days postimmunization. Based on the number of mice with positive vaginal cultures, number of positive cultures, length of time of shedding, and number of inclusion forming units recovered, MOMP vaccinated groups were significantly protected. To assess fertility, when the vaginal cultures became negative, female mice were caged with male mice and the outcome of the pregnancy evaluated. As determined by the number of pregnant mice and the number of embryos, two of the vaccine formulations protected mice up to 180 days postimmunization. To our knowledge this is the first subunit of Chlamydia vaccine that has elicited in mice significant long-term protection against a genital challenge.

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

2012 ◽  
Vol 81 (1) ◽  
pp. 303-310 ◽  
Author(s):  
Paola Massari ◽  
Deana N. Toussi ◽  
Delia F. Tifrea ◽  
Luis M. de la Maza
Keyword(s):  
Chlamydia Trachomatis ◽  
Epithelial Cells ◽  
Membrane Protein ◽  
Host Cell ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Major Outer Membrane Protein ◽  
Host Cells ◽  
Content Type

Chlamydia trachomatisis the most common sexually transmitted bacterial pathogen and the etiologic agent of blinding trachoma. Intracellular signaling pathways leading to host cell inflammation and innate immunity toChlamydiainclude those mediated by Toll-like receptors (TLRs) and nucleotide binding oligomerization domain 1 (Nod1) protein. In epithelial cells, TLR-dependent signaling contributes to local immune responses via induction of inflammatory mediators. There is evidence that TLR3, TLR4, and, particularly, TLR2 are critical forChlamydia-mediated host cell activation and pathology. Despite the importance of TLR2, major chlamydial TLR2 antigens have not been identified so far. Numerous bacterial porins are known TLR2 agonists, i.e., porins fromNeisseriae,Shigella,Salmonella,Haemophilus influenzae, andFusobacterium nucleatum, which share structural and functional similarities with the chlamydial major outer membrane protein (MOMP), a strong antigen candidate for a potential vaccine againstC. trachomatis. We describe the ability of purified, detergent-free MOMP to signal via TLR2in vitroin TLR-overexpressing cells and TLR2-competent human reproductive tract epithelial cell lines. Using MOMP formed in pure protein micelles (proteosomes), we show the induction of TLR2-dependent interleukin-8 (IL-8) and IL-6 secretionin vitro, the involvement of TLR1 as a TLR2 coreceptor, and the activation of both NF-κB and mitogen-activated protein (MAP) kinase intracellular pathways. Interestingly, MOMP proteosomes induce cytokine secretion in endocervical epithelial cells (End/E6E7) but not in urethral epithelial cells (THUECs). A detailed understanding of the TLR2-dependent molecular mechanisms that characterize the effect of MOMP proteosomes on host cells may provide new insights for its successful development as an immunotherapeutic target againstChlamydia.

scholarly journals Characterization of Outer Membrane Proteins in Chlamydia trachomatis LGV Serovar L2

2001 ◽  
Vol 183 (8) ◽  
pp. 2686-2690 ◽  
Author(s):  
Regina J. Tanzer ◽  
Thomas P. Hatch
Keyword(s):  
Chlamydia Trachomatis ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Outer Membrane Proteins ◽  
Major Outer Membrane Protein ◽  
Developmental Cycle ◽  
Reading Frame

ABSTRACT We used a photoactivatable, lipophilic reagent, 3′-(trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine, to label proteins in the outer membrane of elementary bodies ofChlamydia trachomatis LGV serovar L2 and mass spectrometry to identify the labeled proteins. The identified proteins were polymorphic outer membrane proteins E, G, and H, which were made late in the developmental cycle, the major outer membrane protein, and a mixture of 46-kDa proteins consisting of the open reading frame 623 protein and possibly a modified form of the major outer membrane protein.

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