Trachoma Vaccine Studies on Taiwan*

Grayston, J. T.; Woolridge, Robert L.; Wang, San-Pin

doi:10.1111/j.1749-6632.1962.tb30558.x

Cited by 71 publications

(17 citation statements)

References 4 publications

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“…Regardless of how these infection-dependent Ags may contribute to chlamydial pathogenesis, some of these Ags may be important in inducing protective immunity. Consistent with this proposal are the facts that live infection always induces more robust protective immunity than immunization with inactivated organisms in animal models and immunization of humans with inactivated organisms failed to induce long lasting protective immunity against trachoma (7). Indeed, CPAF, a prototype of infection-dependent and immunodominant Ags, was found to induce protective immunity in a mouse model (28,42).…”

Section: Discussionsupporting

confidence: 62%

“…Fortunately, Ag-specific Abs can be used to indirectly monitor the expression of the infection-dependent Ags in humans (27). The facts that inactivated whole chlamydial organism-based vaccines failed to induce protective immunity in humans (7) and live chlamydial organism infection always induces better protective immunity than immunization with inactivated organisms in animal models have led us to hypothesize that some infection-dependent Ags may be able to induce protective responses. This hypothesis is supported by the observation that CPAF, an infection-dependent Ag, has been found to induce protective immunity in mice (28).…”

mentioning

confidence: 99%

“…Vaccination is considered the most effective means for preventing chlamydial infection and diseases. However, the inactivated whole organismbased vaccines failed in human trachoma vaccine trials (6,7). Thus, extensive efforts were made to develop effective and safe subunit vaccines in past decades.…”

mentioning

confidence: 99%

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A Genome-Wide Profiling of the Humoral Immune Response to Chlamydia trachomatis Infection Reveals Vaccine Candidate Antigens Expressed in Humans

Wang

Zhang

et al. 2010

The Journal of Immunology

124

177

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A whole genome scale proteome array consisting of 908 open reading frames encoded in Chlamydia trachomatis genome and plasmid was used to profile anti-chlamydial Ab responses. A total of 719 chlamydial proteins was recognized by one or more antisera from 99 women urogenitally infected with C. trachomatis. Revealing such a large C. trachomatis ANTIGENome in humans might partially be attributed to the significantly improved detection sensitivity of the whole genome scale proteome array assay because both linear and conformation-dependent Abs were detected by the array assay. Twenty-seven of the 719 Ags were recognized by ≥50% antisera, thus designated as immunodominant Ags. Comparison of Ag profiles recognized by live chlamydial organism-infected versus dead organism-immunized hosts led to the identification of infection-dependent or in vivo expressed Ags. The infection-dependent Ags induced Abs only in live organism-infected, but not in dead organism-immunized hosts. Many of these Ags were highly expressed during replication, but only minimally packaged into the infectious elementary bodies. Because inactivated whole chlamydial organism-based vaccines failed to induce protection in humans, identification of the infection-dependent or in vivo expressed immunodominant Ags in humans should greatly facilitate the selection of promising chlamydial subunit vaccine candidates for further evaluation. This approach may also be applicable to other pathogens.

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Section: Discussionsupporting

confidence: 62%

mentioning

confidence: 99%

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A Genome-Wide Profiling of the Humoral Immune Response to Chlamydia trachomatis Infection Reveals Vaccine Candidate Antigens Expressed in Humans

Wang

Zhang

et al. 2010

The Journal of Immunology

124

177

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“…Significantly more mice shed in the anti-CD4+ treated group when compared to non-treated group at D21 (62% vs 0%) and onward (D28: 50%, D35: 37%, D42: 25% vs 0%) (P<0.05). In the CD4+ T-cell depleted group there was an increase in length of days of shedding (median days 31.5; range 4–49) versus the non-treated (12; 4–21) and the CD8+ T-cell depleted (9; 4–28) groups (P<0.05). Also, during the six weeks of the experiment, there is a statistically significant difference (P<0.05) between the total number of positive vaginal cultures in the CD4+ T-cell depleted group (60.9%; 39/64), versus the non-treated (26.6%; 34/128) and the CD8+ T-cell depleted (23.4%; 15/64) groups.…”

Section: Resultsmentioning

confidence: 94%

Increased Immunoaccessibility of MOMP Epitopes in a Vaccine Formulated with Amphipols May Account for the Very Robust Protection Elicited against a Vaginal Challenge with Chlamydia muridarum

Tifrea

Pal

Popot

et al. 2014

The Journal of Immunology

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There is a need to implement a vaccine to protect against Chlamydia trachomatis infections. To test a new vaccine mice were immunized with the C. muridarum native major outer membrane protein (nMOMP) solubilized with either amphipol A8-35 or the detergent Z3-14. Ovalbumin was used as a negative control and mice inoculated intranasally with C. muridarum as positive controls. Animals vaccinated with nMOMP mounted strong Chlamydia-specific humoral and cell mediated immune responses. Mice vaccinated with nMOMP/A8-35 had a higher ratio of antibodies to denatured EB over live EB, recognized more synthetic MOMP peptides and had higher neutralizing titers than sera from mice immunized with nMOMP/Z3-14. T-cell lymphoproliferative responses and levels of IFN-γ were also higher in mice vaccinated with nMOMP/A8-35 than with nMOMP/Z3-14. Following immunization animals were challenged intravaginally with C. muridarum. Based on the number of mice with positive vaginal cultures, length of vaginal shedding, total number of positive vaginal cultures and number of Chlamydia inclusion forming units recovered, nMOMP/A8-35 elicited a more robust protection than nMOMP/Z3-14. By depleting T-cells with antibodies we determined that CD4+ and not CD8+ T-cells, mediated the protection elicited by nMOMP/A8-35. Mice were subsequently mated and based on the number of pregnant mice and number of embryos, animals vaccinated with nMOMP/A8-35 or nMOMP/Z3-14 had fertility rates equivalent to the positive control group immunized with live EB and the fertility controls. In conclusion, increased accessibility of epitopes in the nMOMP/A8-35 preparation may account for the very robust protection against infection and disease elicited by this vaccine.

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“…A second (or long-term) solution is vaccination so that exposure to C. trachomatis no longer causes complications. The failure of whole-organism-based vaccines more than 50 years ago (26,27) and immunological studies since then (42)(43)(44) have led to the conclusion that a subunit chlamydial vaccine is both necessary and feasible (52). However, there is still no licensed C. trachomatis vaccine.…”

mentioning

confidence: 99%

A Chlamydia trachomatis OmcB C-Terminal Fragment Is Released into the Host Cell Cytoplasm and Is Immunogenic in Humans

Gong

Lei

et al. 2011

Infect Immun

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The Chlamydia trachomatis outer membrane complex protein B (OmcB) is an antigen with diagnostic and vaccine relevance. To further characterize OmcB, we generated antibodies against OmcB C-terminal (OmcBc) and N-terminal (OmcBn) fragments. Surprisingly, the anti-OmcBc antibody detected dominant signals in the host cell cytosol, while the anti-OmcBn antibody exclusively labeled intrainclusion signals in C. trachomatisinfected cells permeabilized with saponin. Western blot analyses revealed that OmcB was partially processed into OmcBc and OmcBn fragments. The processed OmcBc was released into host cell cytosol, while the OmcBn and remaining full-length OmcB were retained within the chlamydial inclusions. The organism-associated OmcB epitopes became detectable only after the C. trachomatis-infected cells were permeabilized with strong detergents such as SDS. However, the harsh permeabilization conditions also led to the leakage of the already secreted OmcBc and chlamydia-secreted protease (CPAF) out of the host cells. The OmcBc processing and release occurred in all biovars of C. trachomatis. Moreover, the released OmcBc but not the retained OmcBn was highly immunogenic in C. trachomatis-infected women, which is consistent with the concept that exposure of chlamydial proteins to host cell cytosol is accompanied by increased immunogenicity. These observations have provided important information for further exploring/optimizing OmcB as a target for the development of diagnosis methods and vaccines.

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Trachoma Vaccine Studies on Taiwan*

Cited by 71 publications

References 4 publications

A Genome-Wide Profiling of the Humoral Immune Response to Chlamydia trachomatis Infection Reveals Vaccine Candidate Antigens Expressed in Humans

A Genome-Wide Profiling of the Humoral Immune Response to Chlamydia trachomatis Infection Reveals Vaccine Candidate Antigens Expressed in Humans

Increased Immunoaccessibility of MOMP Epitopes in a Vaccine Formulated with Amphipols May Account for the Very Robust Protection Elicited against a Vaginal Challenge with Chlamydia muridarum

A Chlamydia trachomatis OmcB C-Terminal Fragment Is Released into the Host Cell Cytoplasm and Is Immunogenic in Humans

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