High-throughput proteomic screening identifies Chlamydia trachomatis antigens that are capable of eliciting T cell and antibody responses that provide protection against vaginal challenge

Picard, Michele; Cohane, Kenya Prince; Gierahn, Todd M.; Higgins, Darren E.; Flechtner, Jessica B.

doi:10.1016/j.vaccine.2012.01.017

Cited by 29 publications

(16 citation statements)

References 23 publications

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“…As chlamydial infection causes host cell DNA fragmentation and aberrant chromosomal segregation in dividing cells (39,(54)(55)(56), it is more likely that the contribution to carcinogenesis is based on DNA damage mechanisms rather than on MHC I subversion. The development of a C. trachomatis T cell vaccine is the current focus of many research groups (57)(58)(59). Although effective antimicrobial therapies exist, vaccination is considered to be the best approach by which to reduce the prevalence of chlamydial infections (57,60).…”

Section: Discussionmentioning

confidence: 99%

Chlamydia trachomatis-Infected Epithelial Cells and Fibroblasts Retain the Ability To Express Surface-Presented Major Histocompatibility Complex Class I Molecules

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Chlamydia trachomatis-Infected Epithelial Cells and Fibroblasts Retain the Ability To Express Surface-Presented Major Histocompatibility Complex Class I Molecules

et al. 2014

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“…(i) CBA and IFN-␥ enzyme-linked immunosorbent spot (ELISPOT) assays. Antigen-specific IFN-␥-positive CD4 ϩ and CD8 ϩ T cells were detected and quantitated as previously described (30). Briefly, splenic CD4 ϩ and CD8 ϩ T cells, derived from immunized mice, were enriched by magnetic bead isolation, resuspended at a final concentration of 4 ϫ 10 6 /ml in RPMI 1640 medium (Mediatech, Manassas, VA) supplemented with 10% (vol/vol) heat-inactivated FBS (HyClone, Logan, UT), 100 U penicillin, and 100 g streptomycin per ml, 2 mM L-glutamine, 1 mM sodium pyruvate (Mediatech), and 55 M ␤-mercaptoethanol (Invitrogen Life Technologies), and plated at a density of 2 ϫ 10 5 cells per well on polyvinylidene difluoride (PVDF) membranes (Millipore, Billerica, MA) precoated with anti-mouse IFN-␥ capture antibody (Mabtech, Nacka Strand, Sweden).…”

Section: Cells and Virusesmentioning

confidence: 99%

“…(i) Antigen-specific antibody titers. Antibody titers were determined by standard antigen-specific enzyme-linked immunosorbent assays (ELISA) as previously described (30). Briefly, ELISA plates were coated overnight at 4C°with either 0.5 g/ml gD2⌬TMR or 1.5 g/ml ICP4 383-766 protein diluted in coating buffer.…”

Section: Cells and Virusesmentioning

confidence: 99%

An Adjuvanted Herpes Simplex Virus 2 Subunit Vaccine Elicits a T Cell Response in Mice and Is an Effective Therapeutic Vaccine in Guinea Pigs

Škoberne

Cardin

Lee

et al. 2013

J Virol

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bImmunotherapeutic herpes simplex virus 2 (HSV-2) vaccine efficacy depends upon the promotion of antigen-specific immune responses that inhibit reactivation or reactivated virus, thus controlling both recurrent lesions and viral shedding. In the present study, a candidate subunit vaccine, GEN-003/MM-2, was evaluated for its ability to induce a broad-spectrum immune response in mice and therapeutic efficacy in HSV-2-infected guinea pigs. GEN-003 is comprised of HSV-2 glycoprotein D2 (gD2⌬TMR 340-363 ) and a truncated form of infected cell polypeptide 4 (ICP4 383-766 ), formulated with Matrix M-2 (MM-2) adjuvant (GEN-003/MM-2). In addition to eliciting humoral immune responses, CD4؉ and CD8 ؉ T cells characterized by the secretion of multiple cytokines and cytolytic antigen-specific T cell responses that were able to be recalled at least 44 days after the last immunization were induced in immunized mice. Furthermore, vaccination with either GEN-003 or GEN-003/MM-2 led to significant reductions in both the prevalence and severity of lesions in HSV-2-infected guinea pigs compared to those of phosphate-buffered saline (PBS) control-vaccinated animals. While vaccination with MM-2 adjuvant alone decreased recurrent disease symptoms compared to the PBS control group, the difference was not statistically significant. Importantly, the frequency of recurrent viral shedding was considerably reduced in GEN-003/MM-2-vaccinated animals but not in GEN-003-or MM-2-vaccinated animals. These findings suggest a possible role for immunotherapeutic GEN-003/MM-2 vaccination as a viable alternative to chronic antiviral drugs in the treatment and control of genital herpes disease. H erpes simplex virus 2 (HSV-2) is one of the most prevalent sexually transmitted diseases, having infected more than 500 million people worldwide, with an estimated 23 million new infections occurring annually (1). HSV-2 infects epithelial cells of the genital mucosa during primary infection, followed by the establishment of latency in neuronal dorsal root ganglia via retrograde transport along nerve axons. Throughout latency, virus can reactivate, causing genital lesions and/or asymptomatic shedding of virus. Although suppressive antiviral therapy has shown promise in reducing both symptomatic recurrent lesions and overall viral shedding, subclinical HSV reactivation persists, likely contributing significantly to the observed continued transmission (2). The development of an efficacious immunotherapeutic vaccine targeting HSV-2 likely represents the best strategy for preventing both lesion outbreaks and the continued spread of virus.Despite considerable effort, all vaccine candidates to date have failed to meet their defined endpoints in clinical trials. The majority of clinical trials to date have focused on prophylactic subunit vaccines, largely using the HSV-2 surface glycoproteins as immunogens. The viral envelope glycoproteins gD and gB are the dominant targets for neutralizing antibody production (3, 4), making them logical candidates for vaccine devel...

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“…ATLAS has also been applied to the identification of C. trachomatis antigens in mice; the C. trachomatis screening library was first used to identify the specificity of a protective T cell line generated from infected mice (20) and later used to identify the entire repertoire of immunodominant CD4 ϩ and CD8 ϩ T cell antigens elicited during experimental intraperitoneal C. trachomatis infection. When separately formulated with adjuvant as protein subunit vaccines, two of the antigens identified in mice elicited antigen-specific T cells capable of conferring protection against C. trachomatis genital challenge in a mouse infection model (21). While these data were encouraging, antigen specificities and mechanisms of infection may be very disparate between inbred mice and humans; therefore, we hypothesized that the best antigen candidates would be identified through profiling the specificity and nature of T cell responses in samples from human volunteers that have spontaneously cleared natural infection with C. trachomatis.…”

mentioning

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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High-throughput proteomic screening identifies Chlamydia trachomatis antigens that are capable of eliciting T cell and antibody responses that provide protection against vaginal challenge

Cited by 29 publications

References 23 publications

Chlamydia trachomatis-Infected Epithelial Cells and Fibroblasts Retain the Ability To Express Surface-Presented Major Histocompatibility Complex Class I Molecules

Chlamydia trachomatis-Infected Epithelial Cells and Fibroblasts Retain the Ability To Express Surface-Presented Major Histocompatibility Complex Class I Molecules

An Adjuvanted Herpes Simplex Virus 2 Subunit Vaccine Elicits a T Cell Response in Mice and Is an Effective Therapeutic Vaccine in Guinea Pigs

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

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