Cervicovaginal microbial features predict Chlamydia trachomatis spread to the upper genital tract of infected women.

Introduction: Chlamydia trachomatis (CT) infection can lead to pelvic inflammatory disease, infertility and other reproductive sequelae when it ascends to the upper genital tract. Factors including chlamydial burden, co-infection with other sexually-transmitted bacterial pathogens and oral contraceptive use influence risk for upper genital tract spread. Cervicovaginal microbiome composition influences CT susceptibility and we investigated if it contributes to spread by analyzing amplicon sequence variants (ASVs) derived from the V4 region of 16S rRNA genes in vaginal samples collected from women at high risk for CT infection and for whom endometrial infection had been determined.

Diagnostic-avoiding Chlamydia trachomatis variants detected in cervical and endometrial specimens from women during 16S microbiome profiling.

Background: Performance of a 16S rRNA analysis of the cervicovaginal microbiome of 220 participants recruited into the T Cell Response against Chlamydia (TRAC) cohort between February 2011 and August 2014 in Allegheny County, Pennsylvania USA detected DNA encoding chlamydial 16S rRNA in samples from seven participants whose tests were negative for Chlamydia trachomatis (CT) and DNA encoding gonococcal 16S rRNA from five participants whose tests were negative for Neisseria gonorrhoeae (NG) infection with the Aptima Combo2 assay (Hologic).

Methods: We used targeted PCR amplification followed by sequencing to characterize the chlamydial 23S rRNA locus and qPCR to detect gonococcal DNA in residual diagnostic swab eluates or DNA used to generate 16S rRNA libraries.

Results: Discrepant specimens that contained chlamydial DNA carried a diagnostic-avoidant, G1526A variant in the 23S rRNA locus identical to variants previously detected in Finland, Denmark, and the UK.

Intranasal immunization with CPAF combined with ADU-S100 induces an effector CD4 T cell response and reduces bacterial burden following intravaginal infection with Chlamydia muridarum.

Chlamydia trachomatis (Ct) is the most common bacterial sexually transmitted infection globally, and a vaccine is urgently needed to stop transmission and disease. Chlamydial Protease Activity Factor (CPAF) is an immunoprevalent and immunodominant antigen for CD4 T cells and B cells, which makes it a strong vaccine candidate. Due to the tolerogenic nature of the female genital tract (FGT) and its lack of secondary lymphoid tissue, effective induction of protective cell-mediated immunity will likely require potent and safe mucosal adjuvants.

Chlamydia trachomatis induces low-frequency, sustained CD4 T cell responses in most women, predominantly targeting chlamydial protease-like activity factor, CPAF.

Background: Chlamydia trachomatis (CT) is a globally prevalent sexually transmitted infection (STI) that can result in pelvic inflammatory disease, ectopic pregnancy and infertility in women. Currently, there is no prophylactic vaccine.

Methods: This study examined T cell immunity in a cohort of women recently infected with CT.

Viral-vectored boosting of OmcB- or CPAF-specific T-cell responses fail to enhance protection from Chlamydia muridarum in infection-immune mice and elicits a non-protective CD8-dominant response in naïve mice.

A vaccine is needed to combat the Chlamydia epidemic. Replication-deficient viral vectors are safe and induce antigen-specific T-cell memory. We tested the ability of intramuscular immunization with modified vaccinia Ankara (MVA) virus or chimpanzee adenovirus (ChAd) expressing chlamydial outer membrane protein (OmcB) or the secreted protein, chlamydial protease-like activating factor (CPAF), to enhance T-cell immunity and protection in mice previously infected with plasmid-deficient Chlamydia muridarum CM972 and elicit protection in naïve mice.

Unique T cell signatures associated with reduced reinfection in a highly exposed cohort.

(CT) is the most common bacterial sexually transmitted infection globally. Understanding natural immunity to CT will inform vaccine design. This study aimed to profile immune cells and associated functional features in CT-infected women, and determine immune profiles associated with reduced risk of ascended endometrial CT infection and CT reinfection.

Systemic priming and intranasal booster with a BcfA-adjuvanted acellular pertussis vaccine generates CD4+ IL-17+ nasal tissue resident T cells and reduces nasal colonization.

Introduction: Resurgence of pertussis, caused by Bordetella pertussis, necessitates novel vaccines and vaccination strategies to combat this disease. Alum-adjuvanted acellular pertussis vaccines (aPV) delivered intramuscularly reduce bacterial numbers in the lungs of immunized animals and humans, but do not reduce nasal colonization. Thus, aPV-immunized individuals are sources of community transmission.

Genetic susceptibility loci for endometrial infection influence expression of genes involved in T cell function, tryptophan metabolism and epithelial integrity.

Objectives: Identify genetic loci of enhanced susceptibility to upper genital tract infection in women.

Methods: We performed an integrated analysis of DNA genotypes and blood-derived mRNA profiles from 200 exposed women to identify expression quantitative trait loci (eQTL) and determine their association with endometrial chlamydial infection using a mediation test. We further evaluated the effect of a lead eQTL on the expression of by immune cells from women with genotypes associated with low and high whole blood expression of , respectively.

Bps polysaccharide of Bordetella pertussis resists antimicrobial peptides by functioning as a dual surface shield and decoy and converts Escherichia coli into a respiratory pathogen.

Infections and disease caused by the obligate human pathogen Bordetella pertussis (Bp) are increasing, despite widespread vaccinations. The current acellular pertussis vaccines remain ineffective against nasopharyngeal colonization, carriage, and transmission. In this work, we tested the hypothesis that Bordetella polysaccharide (Bps), a member of the poly-β-1,6-N-acetyl-D-glucosamine (PNAG/PGA) family of polysaccharides promotes respiratory tract colonization of Bp by resisting killing by antimicrobial peptides (AMPs).

Colonization Factor A (BcfA) Elicits Protective Immunity against Bordetella bronchiseptica in the Absence of an Additional Adjuvant.

is an etiologic agent of respiratory diseases in animals and humans. Despite the widespread use of veterinary vaccines, there is limited information on their composition and relative efficacy and on the immune responses that they elicit. Furthermore, human vaccines are not available.

Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice.

Vaccines are a 20 century medical marvel. They have dramatically reduced the morbidity and mortality caused by infectious diseases and contributed to a striking increase in life expectancy around the globe. Nonetheless, determining vaccine efficacy remains a challenge.