Vaccination with the<i>Chlamydia trachomatis</i>Major Outer Membrane Protein Can Elicit an Immune Response as Protective as That Resulting from Inoculation with Live Bacteria

Pal, Sukumar; Peterson, Ellena M.; Maza, Luis M. de la

doi:10.1128/iai.73.12.8153-8160.2005

Cited by 161 publications

(225 citation statements)

References 52 publications

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“…Indeed, there are several examples in the Chlamydia field, showing that antigens, including the gold standard vaccine candidate MOMP, perform quite differently, in terms of protection, depending on the adjuvant used in immunization (38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines

Finco

Frigimelica

Buricchi

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Natural immunity against obligate and/or facultative intracellular pathogens is usually mediated by both humoral and cellular immunity. The identification of those antigens stimulating both arms of the immune system is instrumental for vaccine discovery. Although high-throughput technologies have been applied for the discovery of antibody-inducing antigens, few examples of their application for T-cell antigens have been reported. We describe how the compilation of the immunome, here defined as the pool of immunogenic antigens inducing T- and B-cell responses in vivo, can lead to vaccine candidates against Chlamydia trachomatis . We selected 120 C. trachomatis proteins and assessed their immunogenicity using two parallel high-throughput approaches. Protein arrays were generated and screened with sera from C. trachomatis -infected patients to identify antibody-inducing antigens. Splenocytes from C. trachomatis -infected mice were stimulated with 79 proteins, and the frequency of antigen-specific CD4 + /IFN-γ + T cells was analyzed by flow cytometry. We identified 21 antibody-inducing antigens, 16 CD4 + /IFN-γ + –inducing antigens, and five antigens eliciting both types of responses. Assessment of their protective activity in a mouse model of Chlamydia muridarum lung infection led to the identification of seven antigens conferring partial protection when administered with LTK63/CpG adjuvant. Protection was largely the result of cellular immunity as assessed by CD4 + T-cell depletion. The seven antigens provided robust additive protection when combined in four-antigen combinations. This study paves the way for the development of an effective anti- Chlamydia vaccine and provides a general approach for the discovery of vaccines against other intracellular pathogens.

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Section: Discussionmentioning

confidence: 99%

Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines

Finco

Frigimelica

Buricchi

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Although Chlamydia-triggered inflammatory responses are thought to be largely responsible for Chlamydia-induced diseases (4), the precise pathogenic mechanisms remain unclear. A murine biovar of C. trachomatis (known as mouse pneumonitis [MoPn] agent and now classified as a new species, Chlamydia muridarum) has been used to study the mechanisms of C. trachomatis pathogenesis and immunity in a mouse genital infection model (5)(6)(7)(8)(9). Mice intravaginally infected with the C. muridarum organisms can develop inflammatory pathologies including endometritis and hydrosalpinx similar to those in humans (10).…”

mentioning

confidence: 99%

Mice Deficient in MyD88 Develop a Th2-Dominant Response and Severe Pathology in the Upper Genital Tract following Chlamydia muridarum Infection

Chen

Lei

Chang

et al. 2010

The Journal of Immunology

110

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MyD88, a key adaptor molecule required for many innate immunity receptor-activated signaling pathways, was evaluated in a Chlamydia muridarum urogenital tract infection model. Compared with wild-type mice, MyD88 knockout (KO) mice failed to produce significant levels of inflammatory cytokines in the genital tract during the first week of chlamydial infection. MyD88 KO mice developed a Th2-dominant whereas wild-type mice developed a Th1/Th17-dominant immune response after chlamydial infection. Despite the insufficient production of early inflammatory cytokines and lack of Th1/Th17-dominant adaptive immunity, MyD88 KO mice appeared to be as resistant to chlamydial intravaginal infection as wild-type mice based on the number of live organisms recovered from vaginal samples. However, significantly high numbers of chlamydial organisms were detected in the upper genital tract tissues of MyD88 KO mice. Consequently, MyD88 KO mice developed more severe pathology in the upper genital tract. These results together have demonstrated that MyD88-dependent signaling pathway is not only required for inflammatory cytokine production in the early phase of host response to chlamydial infection but also plays a critical role in the development of Th1/Th17 adaptive immunity, both of which may be essential for limiting ascending infection and reducing pathology of the upper genital tract by chlamydial organisms.

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“…The vaccine needs to promote two CMI and antibody response, CAF01 is an adjuvant that is appropriate to enter human clinical trials in future [27]. CPG and Montanide are two other adjuvants that are now in clinical trials [28,29]. In addition, Novel delivery systems, including Vibrio cholerae ghosts and cationic liposomes, may have the potential to elicit protective responses against chlamydial genital infection when used in conjunction with appropriate antigens [30].…”

Section: Discussionmentioning

confidence: 99%

Cloning and Expression of Truncated Chlamydial Major Outer Membrane Protein in E.coli: A Miniature Step Forward

Bitazar¹,

Farivar²,

Hajikhani³

et al. 2014

J Vaccines Vaccin

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Administration of Prophylactic vaccines still is the cutting-edge of prevention, control and elimination of infections. Among the common causes of sexually transmitted diseases, chlamydia trachomatis is an important socioeconomic burden worldwide which impairs human genital tract function, resulting in severe complications like urethritis, pelvic inflammatory disease (PID), getting ease of HIV transmission, playing cofactor role in human papilloma virus (HPV)-induced cervical neoplasia, and unfortunately infertility. Because of all difficulties, vaccination is considered to be the most economical and reliable way to escape from unrestrained exacerbation states of infection than any other prevalence program. But despite much advancement in the field of veterinary, the dream has yet to be realized. Among a number of potential candidates, the major outer membrane protein (MOMP) is a vanguard of subunit vaccines. In this attempt, MOMP217 gene fragment cloned in PET28b+ and expressed in E.coli. The protein expression confirmed by SDS-PAGE. These findings demonstrate that, considering the antigenicity prediction and due to the existence of potential epitopic region, rMOMP217 could be a potential capable peptide which can represent as an alternative to whole MOMP. Journal of Vaccines & Vaccination Cloning of PET-MOMP217PCR was performed to amplify the MOMP217 containing epitopic regions with specific primers. Qiagen gel extraction kit (Qiagen, Hilden, Germany) was used to purify PCR amplified product and plasmid DNA. Purified plasmid and amplified insert were double digested with BamHI and HindIII (Fermentase). The digested products were purified and ligated into linearised and purified vector withT4 DNA ligase enzyme(Fermentase), then ligation mixture were transformed into E.coli DH5α cloning host. As well, Recombinant clones were confirmed by colony PCR and double digestion. The confirmed purified DH5α/ pET-MOMP217 positive colony were transformed and cloned into E.coli BL21 (DE3) expression host and used for protein expression purpose with IPTG. Protein expressionE.coli BL2 (DE3) with T7 promoter, harboring the PET-MOMP217 (24kDa) positive colony were grown in 100 ml LB broth at 37°C including 100 µg/ml kanamycin (Sigma) to achieve an optical density (OD) of 0.7 (stationary growth phase) at 600 nm at this time, 1 mM isopropyl-ß-D-thiogalactoside (IPTG; Invitrogen) were added to 50 ml LB broth and the other same amount were considered as uninduced (-IPTG) control. Incubation was continued at 37°C. The samples from induced and uninduced culture were collected within 2, 4, 6 hours and overnight after induction. Incubation temperature in the case of overnight was reduced to 25°C. Samples were accumulated, centrifuged at 6000 rpm for 5 min. Harvested cells were resuspending with 2x loading protein buffer containing 2-ME, boiled and subjected to SDS-PAGE analysis. Total protein expression trend were evaluated by 10% SDS-PAGE stained with Comassie Brilliant Blue. SDS-PAGE were shown to have one band corresponded t...

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Vaccination with theChlamydia trachomatisMajor Outer Membrane Protein Can Elicit an Immune Response as Protective as That Resulting from Inoculation with Live Bacteria

Cited by 161 publications

References 52 publications

Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines

Approach to discover T- and B-cell antigens of intracellular pathogens applied to the design of Chlamydia trachomatis vaccines

Mice Deficient in MyD88 Develop a Th2-Dominant Response and Severe Pathology in the Upper Genital Tract following Chlamydia muridarum Infection

Cloning and Expression of Truncated Chlamydial Major Outer Membrane Protein in E.coli: A Miniature Step Forward

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