CDSimple™ Human IFN-γ Chemiluminescent ELISA Kit

Background: Vaccine-development research is proliferating making it difficult to determine the most promising vaccine candidates. Exemplary of this problem is vaccine development against Chlamydia, a pathogen of global public health and financial importance. Methods: We systematically extracted data from studies that included chlamydial load or host immune parameter measurements, estimating 4,453 standardized effect sizes between control and chlamydial immunization experimental groups. Results: Chlamydial immunization studies most often used (78%) laboratory mouse models. Depending on chlamydial species, single and multiple recombinant protein, viral and bacterial vectors, dendritic transfer, and dead whole pathogen were most effective at reducing chlamydial load. Immunization-driven decrease in chlamydial load was associated with increases in IFNg, IgA, IgG1, and IgG2a. Using data from individual studies, the magnitude of IgA and IgG2a increase was correlated with chlamydial load reduction. IFNg also showed this pattern for C. trachomatis, but not for C. muridarum. We also reveal the chlamydial vaccine development field to be highly bias toward studies showing these effects, limiting lessons learned from negative results. Conclusions: Most murine immunizations against Chlamydia reduced chlamydial load and increased host immune parameters. These methods are novel for vaccine development and are critical in identifying trends where large quantities of literature exist.

Tumours evade immune control by creating hostile microenvironments that perturb T cell metabolism and effector function(1-4). However, it remains unclear how intra-tumoral T cells integrate and interpret metabolic stress signals. Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies(5-8)-induces endoplasmic reticulum stress and activates the IRE1 alpha-XBP1 arm of the unfolded protein response(9,10) in T cells to control their mitochondrial respiration and anti-tumour function. In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression. Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1 alpha-XBP1 activation that suppressed mitochondrial activity and IFN-gamma production. Mechanistically, induction of XBP1 regulated the abundance of glutamine carriers and thus limited the influx of glutamine that is necessary to sustain mitochondrial respiration in T cells under glucose-deprived conditions. Restoring N-linked protein glycosylation, abrogating IRE1 alpha-XBP1 activation or enforcing expression of glutamine transporters enhanced mitochondrial respiration in human T cells exposed to ovarian cancer ascites. XBP1-deficient T cells in the metastatic ovarian cancer milieu exhibited global transcriptional reprogramming and improved effector capacity. Accordingly, mice that bear ovarian cancer and lack XBP1 selectively in T cells demonstrate superior anti-tumour immunity, delayed malignant progression and increased overall survival. Controlling endoplasmic reticulum stress or targeting IRE1 alpha-XBP1 signalling may help to restore the metabolic fitness and anti-tumour capacity of T cells in cancer hosts.