Towards a safe and effective chlamydial vaccine: Lessons from the eye

Mabey, David; Hu, Victor; Bailey, Robin L.; Burton, Matthew J.; Holland, Martin J.

doi:10.1016/j.vaccine.2013.10.016

Cited by 58 publications

(45 citation statements)

References 96 publications

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“…Of concern, C. trachomatis infection in some primates resulted in more severe disease with worse inflammation post-vaccination demonstrating a role for incomplete immunity in enhanced inflammatory pathology [9,10]. However a critical analysis of human trachoma vaccine trials failed to demonstrate similar vaccine immunopathology in humans [11]. Nonetheless concern about exacerbated inflammatory pathology in previously vaccinated non-human primates has continued to be a barrier that impedes human Chlamydia vaccine trial research.…”

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confidence: 99%

Subunit vaccines for the prevention of mucosal infection with Chlamydia trachomatis

Karunakaran

Jiang

et al. 2016

Expert Review of Vaccines

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Chlamydia trachomatis is the most common preventable cause of tubal infertility in women. In high-income countries, despite public health control efforts, C. trachomatis case rates continue to rise. Most medium and low-income countries lack any Chlamydia control program; therefore, a vaccine is essential for the control of Chlamydia infections. A rationally designed Chlamydia vaccine requires understanding of the immunological correlates of protective immunity, pathological responses to this mucosal pathogen, identification of optimal vaccine antigens and selection of suitable adjuvant delivery systems that engender protective immunity. Fortunately, Chlamydia vaccinology is facilitated by genomic knowledge and by murine models that reproduce many of the features of human C. trachomatis infection. This article reviews recent progress in these areas with a focus on subunit vaccine development.

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confidence: 99%

Subunit vaccines for the prevention of mucosal infection with Chlamydia trachomatis

Karunakaran

Jiang

et al. 2016

Expert Review of Vaccines

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“…The trachoma vaccine trials were conducted using whole inactivated C. trachomatis elementary body (EB) preparations, which induced only partial and short-lived protection against infection (5). Importantly, these studies also reported evidence of disease exacerbation, likely due to immunemediated inflammation and tissue damage (6). These deleterious responses could not be unequivocally recapitulated in subsequent nonhuman primate studies (7).…”

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confidence: 99%

Resolution of Chlamydia trachomatis Infection Is Associated with a Distinct T Cell Response Profile

Picard

Bodmer

Gierahn

et al. 2015

Clin Vaccine Immunol

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dChlamydia trachomatis is the causative agent of the most frequently reported bacterial sexually transmitted infection, the total burden of which is underestimated due to the asymptomatic nature of the infection. Untreated C. trachomatis infections can cause significant morbidities, including pelvic inflammatory disease and tubal factor infertility (TFI). The human immune response against C. trachomatis, an obligate intracellular bacterium, is poorly characterized but is thought to rely on cell-mediated immunity, with CD4؉ and CD8 ؉ T cells implicated in protection. In this report, we present immune profiling data of subjects enrolled in a multicenter study of C. trachomatis genital infection. CD4؉ and CD8 ؉ T cells from subjects grouped into diseasespecific cohorts were screened using a C. trachomatis proteomic library to identify the antigen specificities of recall T cell responses after natural exposure by measuring interferon gamma (IFN-␥) levels. We identified specific T cell responses associated with the resolution of infection, including unique antigens identified in subjects who spontaneously cleared infection and different antigens associated with C. trachomatis-related sequelae, such as TFI. These data suggest that novel and unique C. trachomatis T cell antigens identified in individuals with effective immune responses can be considered as targets for vaccine development, and by excluding antigens associated with deleterious sequelae, immune-mediated pathologies may be circumvented.

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“…121 Finally, as noted by Mabey et al, "an important difference between ocular and genital infection is that in the eye the damaging sequelae occur at the site of infection, the conjunctival epithelium" while "by contrast in the female genital tract, the major sequelae develop in the fallopian tubes and not at the cervix, which is the site of inoculation". 80 Nevertheless, the pathology of C. trachomatis infection is similar in the eye and genital tract and involves a complex interaction of innate and adaptive immune responses to the organism that influence both protection and pathology in ocular and sexually transmitted chlamydial infections. Vaccine efforts against this intracellular pathogen will need to ensure that any immune responses generated by the ocular and genital vaccines will include the appropriate populations of innate, B, and T-cells that will engender protection and minimize pathology in the host.…”

Section: Acquired Immunity and Pathologymentioning

confidence: 99%

“…Several of these newly characterized virulence targets are being evaluated as potential vaccine candidates. 80 While the chlamydial genetic toolbox has expanded significantly over the past few years, it is likely to continue to become easier and easier to manipulate Chlamydia, with both forward and reverse genetics now being possible (eg, targetron approach), and more advanced techniques such as conditional gene silencing and transposon mutagenesis not far off.…”

Section: The Choice Of Immunogenic Target Antigens Is Rapidly Expandingmentioning

confidence: 99%

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Development of a vaccine for Chlamydia trachomatis: challenges and current progress

Hafner¹

2015

VDT

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Abstract:Chlamydia trachomatis remains an enigmatic bacterial pathogen with no vaccine yet available to treat human ocular and genital tract infections caused by tissue-tropic serovars of the organism. Globally, it is the leading cause of preventable blindness as well as the leading cause of bacterial sexually transmitted infections. The pathogen has a range of virulence factors that enable it to successfully evade both the innate and adaptive immune system of the host. The host immune system, although protective, paradoxically is also associated closely with the pathologies of trachoma and pelvic inflammatory disease -disease sequelae of some chlamydial infections and reinfections in some genetically susceptible hosts. In this review, we focus on what is known currently about the pathogenesis of ocular and genital infections caused by this mucosal pathogen. We also discuss novel insights into the pathogenesis of infections caused by the genital and ocular serovars of C. trachomatis, including a discussion of both pathogen and host factors, such as the human microbiota at these mucosal sites as well as the current immunological challenges facing vaccine development. Finally, we discuss the current progress toward development of a vaccine against C. trachomatis. A wide range of recombinant protein antigens are being identified and, hence, are available for vaccine trials. A plasmid-free live strain has recently been produced and evaluated in the mouse (Chlamydia muridarum) and monkey (C. trachomatis) models. The data for ocular infections in the monkey model was particularly encouraging, although the path to regulatory approval of a live vaccine is still uncertain. While still a major challenge, vaccines for ocular and genital C. trachomatis infections are looking more promising.

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Towards a safe and effective chlamydial vaccine: Lessons from the eye

Cited by 58 publications

References 96 publications

Subunit vaccines for the prevention of mucosal infection with Chlamydia trachomatis

Subunit vaccines for the prevention of mucosal infection with Chlamydia trachomatis

Resolution of Chlamydia trachomatis Infection Is Associated with a Distinct T Cell Response Profile

Development of a vaccine for Chlamydia trachomatis: challenges and current progress

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