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Prophylactic Multi-Subunit Vaccine against Chlamydia trachomatis: In Vivo Evaluation in Mice.

ABSTRACT: Chlamydia trachomatis is the most frequent sexually-transmitted disease-causing bacterium. Urogenital serovars of this intracellular pathogen lead to urethritis and cervicitis. Ascending infections result in pelvic inflammatory disease, salpingitis, and oophoritis. One of 200 urogenital infections leads to tubal infertility. Serovars A-C cause trachoma with visual impairment. There is an urgent need for a vaccine. We characterized a new five-component subunit vaccine in a mouse vaccination-lung challenge infection model. Four recombinant Pmp family-members and Ctad1 from C. trachomatis serovar E, all of which participate in adhesion and binding of chlamydial elementary bodies to host cells, were combined with the mucosal adjuvant cyclic-di-adenosine monophosphate. Intranasal application led to a high degree of cross-serovar protection against urogenital and ocular strains of C. trachomatis, which lasted at least five months. Critical evaluated parameters were body weight, clinical score, chlamydial load, a granulocyte marker and the cytokines IFN-γ/TNF-α in lung homogenate. Vaccine antigen-specific antibodies and a mixed Th1/Th2/Th17 T cell response with multi-functional CD4⁺ and CD8⁺ T cells correlate with protection. However, serum-transfer did not protect the recipients suggesting that circulating antibodies play only a minor role. In the long run, our new vaccine might help to prevent the feared consequences of human C. trachomatis infections.

SUBMITTER: Lanfermann C

PROVIDER: S-EPMC8226540 | biostudies-literature |

REPOSITORIES: biostudies-literature

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In silico vaccine design against Chlamydia trachomatis infection.

Project description:Chlamydia trachomatis, a gram-negative bacterium known to infect the genital sites mainly columnar epithelial cells of the cervix, urethra and rectum in women and causes acute epididymitis, urinary tract inflammation and DNA damage to the sperms in men, hence considered to be one of the major sexually transmitted infections. The infection is asymptomatic in many people and remains untreated leading to serious health complications, including pelvic inflammatory disease, ectopic pregnancy and infertility. The current treatment options include antibiotics, but the pathogen has gained resistance against many antibiotics. The present work involves an in silico reverse vaccinology approach for identifying the immunogens as vaccine candidates that can be effective against reinfections and should be capable of inducing long-term protective immunity against Chlamydial infections. This study identifies the putative vaccine candidates that are membrane bound with high antigenicity properties; antigenicity induces the immunogenicity which involves identification of T-cell and B-cell epitopes that induce both humoral and cell-mediated immunity. The epitopes 'LSWEMELAY', 'LSNTEGYRY', 'TSDLGQMEY', 'FIDLLQAIY' and 'FSNNFSDIY' were predicted as core sequences for class I MHC molecules. The identified epitopes showed promising ability to interact with the human leukocyte antigens (HLA). These epitopes showed maximum population coverage with epitope conservancy above 80%. Molecular docking was performed to test the binding affinities of the identified epitopes with the HLA molecule to study the binding cleft interactions. The vaccine candidate thus identified from this study showed to possess the potential to activate the B- and T-cell immune responses which are more specific and make the body stronger against infections and effective for reinfections.

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A Recombinant Chlamydia trachomatis MOMP Vaccine Elicits Cross-serogroup Protection in Mice Against Vaginal Shedding and Infertility.

Project description:BackgroundChlamydia trachomatis is the most common sexually transmitted bacterial pathogen worldwide. Here, we determined the ability of a C. trachomatis recombinant major outer membrane protein (rMOMP) vaccine to elicit cross-serogroup protection.MethodsFemale C3H/HeN mice were vaccinated by mucosal and systemic routes with C. trachomatis serovar D (UW-3/Cx) rMOMP and challenged in the ovarian bursa with serovars D (UW-3/Cx), D (UCI-96/Cx), E (IOL-43), or F (N.I.1). CpG-1826 and Montanide ISA 720 were used as adjuvants.ResultsImmune responses following vaccination were more robust against the most closely related serovars. Following a genital challenge (as determined by number of mice with positive vaginal cultures, number of positive cultures, number of inclusion forming units recovered, and number of days with positive cultures) mice challenged with C. trachomatis serovars of the same complex were protected but not those challenged with serovar F (N.I.1) from a different subcomplex. Females were caged with male mice. Based on fertility rates, number of embryos, and hydrosalpinx formation, vaccinated mice were protected against challenges with serovars D (UW-3/Cx), D (UCI-96/Cx), and E (IOL-43) but not F (N.I.1).ConclusionsThis is the first subunit vaccine shown to protect mice against infection, pathology, and infertility caused by different C. trachomatis serovars.

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Maternal immunity partially protects newborn mice against a Chlamydia trachomatis intranasal challenge.

Project description:To determine the role of maternal immunity in protecting newborn mice against a Chlamydia trachomatis infection, female BALB/c mice were immunized intranasally (i.n.) with 10? inclusion forming units (IFU) of the C. trachomatis mouse pneumonitis biovar (MoPn). As a control, another group of female mice was sham-immunized i.n. with HeLa cell extracts. Immunized animals mounted strong immune responses as evidenced by high Chlamydia-specific antibody titers in serum and milk. Newborn mice born from immunized and sham-immunized dams were challenged i.n. with 10³IFU of MoPn at two post-natal days (PND). Following inoculation, newborn mice were euthanized at 7- and 18-PND and the lungs, spleen and intestine were cultured for Chlamydia. Overall, no significant differences were observed between the mice born from and fed by immunized dams and mice born from and fed by sham-immunized dams. Of the mice born from immunized dams, 75 and 25% had positive lung cultures at 7- and 18-PND, respectively. Of the mice born from sham-immunized dams, 82 and 50% had positive lung cultures for those same days. When the number of IFU recovered from the lungs and spleens was compared between the two groups no significant differences were observed. However, when the number of IFU recovered from the small intestine was compared, significant differences were observed between the two groups of newborn mice (2×10? versus 32×10? at 7-PND and 9.2×10? versus 85×10? at 18-PND). In conclusion, maternal immunity plays a limited role in protecting newborn mice against a Chlamydia infection.

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Protective Effect of Vaccine Promoted Neutralizing Antibodies against the Intracellular Pathogen Chlamydia trachomatis.

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VACCINES. A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells.

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A multi-subunit Chlamydia vaccine inducing neutralizing antibodies and strong IFN-?? CMI responses protects against a genital infection in minipigs.

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