Immune response to the Chlamydia trachomatis outer membrane protein PorB

Kawa, Diane; Schachter, Julius; Stephens, Richard S.

doi:10.1016/j.vaccine.2004.04.035

Cited by 23 publications

(15 citation statements)

References 22 publications

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“…The surface exposure of the less variable PmpC and PmpI proteins is not known, and nothing is known of their immunogenic potential. The PorB protein is surface exposed but appears not to be a natural target for the immune response (22); this may account for its relatively low level of replacement substitution, a level only marginally higher than that seen for the genes encoding the housekeeping enzyme. The pattern of nucleotide substitution in the noncoding regions suggests that they may also be under selection pressure, presumably to conserve regulatory element binding sites.…”

Section: Discussionmentioning

confidence: 99%

TheompAGene inChlamydia trachomatisDiffers in Phylogeny and Rate of Evolution from Other Regions of the Genome

Brunelle

Sensabaugh

2006

Infect Immun

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Strains of Chlamydia trachomatis are classified into serovars based on nucleotide sequence differences in ompA, the gene that encodes the major outer membrane protein. Phylogenetic characterization of strains based on ompA, however, results in serovar groupings that are inconsistent with the distinguishing features of C. trachomatis pathobiology, e.g., tissue tropisms and disease presentation. We have compared nucleotide sequences at multiple sites distributed around the chlamydial genome from 18 strains representing 16 serovars; sampled regions included genes encoding housekeeping enzymes (totaling 2,073 bp), intergenic noncoding segments (1,612 bp), and a gene encoding a second outer membrane protein ( porB; 1,023 bp), with the ompA sequence (1,194 bp) used for reference. These comparative analyses revealed substantial variation in nucleotide substitution patterns among the sampled regions, with average pairwise sequence differences ranging from 0.15% for the housekeeping genes to 12.1% for ompA. Phylogenetic characterization of the sampled genomic sequences yielded a strongly supported tree that divides the strains into groupings consistent with C. trachomatis biology and which has a topology quite distinct from the ompA tree. This phylogenetic incongruity can be accounted for by recombination of the ompA gene between different genomic backgrounds. We found, however, no evidence of recombination within or between any of the sampled regions around the C. trachomatis genome apart from ompA. Parallel analysis of published sequence data on four members of the pmp gene family are consistent with the phylogenetic analyses reported here.

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Section: Discussionmentioning

confidence: 99%

TheompAGene inChlamydia trachomatisDiffers in Phylogeny and Rate of Evolution from Other Regions of the Genome

Brunelle

Sensabaugh

2006

Infect Immun

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“…Additional Inc proteins as well as putative inclusion proteins have also been assessed for their immunogenicity and protective effect, but the results are not as promising as those obtained with MOMP vaccines (30,53,54,97). Porin protein B (PorB) (43,44), the small chain of ribonucleoside reductase (NrdB) (3), and PmpD (20) are all recognized by serum from C. trachomatis-infected patients, and immune serum and/or monoclonal antibodies specific to these proteins are able to neutralize infection in vitro (3,20). Vaccination with PorB results in partial protection against genital challenge, and protection is increased when MOMP is included as part of a subunit vaccine with Vibrio cholerae ghosts (38).…”

Section: Antigensmentioning

confidence: 99%

Vaccination againstChlamydiaGenital Infection Utilizing the MurineC. muridarumModel

2011

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2Chlamydia trachomatis genital infection is a worldwide public health problem, and considerable effort has been expended on developing an efficacious vaccine. The murine model of C. muridarum genital infection has been extremely useful for identification of protective immune responses and in vaccine development. Although a number of immunogenic antigens have been assessed for their ability to induce protection, the majority of studies have utilized the whole organism, the major outer membrane protein (MOMP), or the chlamydial protease-like activity factor (CPAF). These antigens, alone and in combination with a variety of immunostimulatory adjuvants, have induced various levels of protection against infectious challenge, ranging from minimal to nearly sterilizing immunity. Understanding of the mechanisms of natural infection-based immunity and advances in adjuvant biology have resulted in studies that are increasingly successful, but a vaccine licensed for use in humans has not yet been brought to fruition. Here we review immunity to chlamydial genital infection and vaccine development using the C. muridarum model.Chlamydia trachomatis, a Gram-negative obligate intracellular bacterium with a tropism for mucosal epithelial cells, is the most common cause of bacterial sexually transmitted disease in both developed and developing countries, with more than 90 million new cases occurring each year (113-115). More than 4 million new cases of C. trachomatis infection occur each year in the United States, where costs associated with treating those infections and associated complications are in excess of $2 billion annually (107). In the genital tract, infection with C. trachomatis is propagated within the single-cell columnar layer of the epithelium in the urethra of men and the endocervix of women. Within the epithelial cells, C. trachomatis undergoes a unique biphasic developmental cycle consisting of an infectious, but metabolically inert elementary body (EB) and a noninfectious, but metabolically active reticulate body (RB). After completion of the developmental cycle, the EBs are released and infect neighboring epithelial cells, thereby spreading the infection.Infection can result in acute inflammation characterized by redness, edema, and mucosal discharge and is diagnosed clinically as mucopurulent cervicitis in women and nongonococcal urethritis in men (10, 85). In women, infection can manifest as abnormal vaginal discharge and/or postcoital bleeding, while the infection is limited to the lower genital tract, and irregular uterine bleeding and/or pelvic discomfort once the infection ascends to the upper genital tract (85). Symptoms in males are generally limited to dysuria and moderate clear-to-whitish discharge (85). While these symptoms signify an infection, the absence of such symptoms does not necessarily indicate the absence of infection. It is estimated that Ͼ70% of women and 50% of men experience asymptomatic infections (15,113). Without symptoms providing the impetus, asymptomatic individuals may not seek ...

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“…Subunit antigen vaccines represent the bulk of vaccine studies, and vaccines based on combinations of a number of chlamydial antigens, adjuvants, and delivery systems have had various degrees of success in preventing infection (8,22,62). Chlamydial antigens, including secreted proteins, such as chlamydial protease-like activity factor (CPAF) (16,33,(43)(44)(45)(46), and membrane associated proteins, such as PorB (26,30) and IncA (33), have also been used in subunit vaccines; however, the vast majority of studies have focused on the major outer membrane protein (MOMP), an immunodominant antigen in both human and animal studies (22,62). Novel delivery systems, including Vibrio cholerae ghosts and cationic liposomes, have been introduced into chlamydial vaccine research, and while initial studies have shown incomplete protection, these systems may have the potential to elicit protective responses against chlamydial genital infection when used in conjunction with appropriate antigens (2,19,20,23).…”

mentioning

confidence: 99%

CD4⁺T Cells and Antibody Are Required for Optimal Major Outer Membrane Protein Vaccine-Induced Immunity toChlamydia muridarumGenital Infection

Farris

Morrison

2010

Infect Immun

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Despite effective antimicrobial chemotherapy, control of Chlamydia trachomatis urogenital infection will likely require a vaccine. We have assessed the protective effect of an outer membrane protein-based vaccine by using a murine model of chlamydial genital infection. Female mice were first vaccinated with Chlamydia muridarum major outer membrane protein (MOMP) plus the adjuvants CpG-1826 and Montanide ISA 720; then they were challenged with C. muridarum. Vaccinated mice shed 2 log 10 to 3 log 10 fewer inclusion-forming units (IFU) than ovalbumin-vaccinated or naïve animals, resolved infection sooner, and had a lower incidence of hydrosalpinx. To determine the relative contribution of T cells to vaccine-induced protection, mice were vaccinated, depleted of CD4 ؉ or CD8 ؉ T cells, and then challenged vaginally with C. muridarum. Depletion of CD4 ؉ T cells, but not depletion of CD8 ؉ T cells, diminished vaccine-induced protection, with CD4-depleted mice shedding 2 log 10 to 4 log 10 more IFU than CD8-depleted or nondepleted mice. The contribution of antibodies to vaccine-induced protection was demonstrated by the absence of protective immunity in vaccinated B-cell-deficient mice and by a 2 log 10 to 3 log 10 decrease in bacterial shedding by mice passively administered an anti-MOMP serum. Thus, optimal protective immunity in this model of vaccine-induced protection depends on contributions from both CD4 ؉ T cells and antibody.

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Immune response to the Chlamydia trachomatis outer membrane protein PorB

Cited by 23 publications

References 22 publications

TheompAGene inChlamydia trachomatisDiffers in Phylogeny and Rate of Evolution from Other Regions of the Genome

TheompAGene inChlamydia trachomatisDiffers in Phylogeny and Rate of Evolution from Other Regions of the Genome

Vaccination againstChlamydiaGenital Infection Utilizing the MurineC. muridarumModel

CD4⁺T Cells and Antibody Are Required for Optimal Major Outer Membrane Protein Vaccine-Induced Immunity toChlamydia muridarumGenital Infection

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Immune response to the Chlamydia trachomatis outer membrane protein PorB

Cited by 23 publications

References 22 publications

TheompAGene inChlamydia trachomatisDiffers in Phylogeny and Rate of Evolution from Other Regions of the Genome

TheompAGene inChlamydia trachomatisDiffers in Phylogeny and Rate of Evolution from Other Regions of the Genome

Vaccination againstChlamydiaGenital Infection Utilizing the MurineC. muridarumModel

CD4+T Cells and Antibody Are Required for Optimal Major Outer Membrane Protein Vaccine-Induced Immunity toChlamydia muridarumGenital Infection

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Product

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CD4⁺T Cells and Antibody Are Required for Optimal Major Outer Membrane Protein Vaccine-Induced Immunity toChlamydia muridarumGenital Infection