Structural Assessment of Major Outer Membrane Protein (MOMP)-Derived Vaccine Antigens and Immunological Profiling in Mice with Different Genetic Backgrounds.

() is the most common cause of bacterial sexually transmitted infections (STIs) worldwide. infections are often asymptomatic in women, leading to severe reproductive tract sequelae. Development of a vaccine against is crucial.

In Vitro Pre-Clinical Evaluation of a Gonococcal Trivalent Candidate Vaccine Identified by Transcriptomics.

Gonorrhea, a sexually transmitted disease caused by , poses a significant global public health threat. Infection in women can be asymptomatic and may result in severe reproductive complications. Escalating antibiotic resistance underscores the need for an effective vaccine.

Epidemiological and Clinical Observations of Gonococcal Infections in Women and Prevention Strategies.

is rapidly developing antimicrobial resistance. There is an urgent need for an effective gonococcal vaccine. In this study we examined epidemiological and clinical factors associated with gonorrhea in a cohort of women exposed to men with gonococcal urethritis attending the National Center for STD Control clinic in Nanjing, China, to understand the natural history and the risk factors for gonorrhea in this vulnerable population.

Protection against a chlamydial respiratory challenge by a chimeric vaccine formulated with the major outer membrane protein variable domains using the porin B as a scaffold.

is the most frequently detected sexually transmitted bacterial pathogen in the world. Attempts to control these infections with screening programs and antibiotics have failed and, therefore, a vaccine is the best approach to control this epidemic. The major outer membrane protein (MOMP) is the most protective subunit vaccine so far tested.

Neisseria gonorrhoeae Population Genomics: Use of the Gonococcal Core Genome to Improve Surveillance of Antimicrobial Resistance.

Background: Gonorrhea, caused by the bacterium Neisseria gonorrhoeae, is a globally prevalent sexually transmitted infection. The dynamics of gonococcal population biology have been poorly defined due to a lack of resolution in strain typing methods.

Methods: In this study, we assess how the core genome can be used to improve our understanding of gonococcal population structure compared with current typing schemes.

Global Network Analysis of Neisseria gonorrhoeae Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection.

is a Gram-negative diplococcus that is responsible for the sexually transmitted infection gonorrhea, a high-morbidity disease in the United States and worldwide. Over the past several years, strains resistant to antibiotics used to treat this infection have begun to emerge across the globe. Thus, new treatment strategies are needed to combat this organism.

Integrated Bioinformatic Analyses and Immune Characterization of New Vaccine Antigens Expressed during Natural Mucosal Infection.

There is an increasingly severe trend of antibiotic-resistant strains worldwide and new therapeutic strategies are needed against this sexually-transmitted pathogen. Despite the urgency, progress towards a gonococcal vaccine has been slowed by a scarcity of suitable antigens, lack of correlates of protection in humans and limited animal models of infection. gene expression levels in the natural human host does not reflect expression in vitro, further complicating in vitro-basedvaccine analysis platforms.

Evolution of the exclusively human pathogen : Human-specific engagement of immunoregulatory Siglecs.

causes the sexually transmitted disease gonorrhea exclusively in humans and uses multiple strategies to infect, including acquisition of host sialic acids that cap and mask lipooligosaccharide termini, while restricting complement activation. We hypothesized that gonococci selectively target human anti-inflammatory sialic acid-recognizing Siglec receptors on innate immune cells to blunt host responses and that pro-inflammatory Siglecs and pseudogene polymorphisms represent host evolutionary adaptations to counteract this interaction. can indeed engage multiple human but not chimpanzee CD33rSiglecs expressed on innate immune cells and in the genitourinary tract--including Siglec-11 (inhibitory) and Siglec-16 (activating), which we detected for the first time on human cervical epithelium.

Transcriptome Analysis of Neisseria gonorrhoeae during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women.

is a bacterial pathogen responsible for the sexually transmitted infection gonorrhea. Emergence of antimicrobial resistance (AMR) of worldwide has resulted in limited therapeutic choices for this infection. Men who seek treatment often have symptomatic urethritis; in contrast, gonococcal cervicitis in women is usually minimally symptomatic, but may progress to pelvic inflammatory disease.

Structural and Immunological Characterization of Novel Recombinant MOMP-Based Chlamydial Antigens.

is the most common cause of bacterial sexually transmitted infections worldwide. While infections resolve with antibiotic treatment, this is often neglected in women due to frequent asymptomatic infections, leading to disease progression and severe sequelae (pelvic inflammatory disease, ectopic pregnancy, infertility). Development of a vaccine against is crucial.

The ironclad truth: how in vivo transcriptomics and in vitro mechanistic studies shape our understanding of Neisseria gonorrhoeae gene regulation during mucosal infection.

Neisseria gonorrhoeae is one of the most prevalent sexually transmitted infections worldwide. This obligate human pathogen has been extensively studied in vitro, where bacterial factors that are known to contribute to gonococcal disease and their regulation are relatively well defined. However, these in vitro experimental conditions only loosely replicate the host specific environment encountered by the bacteria in vivo.

Neisseriae internalization by epithelial cells is enhanced by TLR2 stimulation.

Neisseria meningitidis (NM) is an opportunistic gram-negative human pathogen that colonizes the human nasopharyngeal epithelium. Asymptomatic carriage is common, but some meningococcal strains can invade nasopharyngeal epithelial cells and proceed to cause severe and often fatal infections. Invasion is predominantly driven by expression of bacterial virulence factors and host cell cognate receptors for bacterial recognition.

Typing and surface charges of the variable loop regions of PorB from Neisseria meningitidis.

PorB is a pan-Neisserial major outer membrane protein with a trimeric β-barrel structure. Each monomer presents eight periplasmic turns and eight surface exposed loop regions with sequence variability. PorB induces activation of host cell responses via a TLR2-dependent mechanism likely mediated by electrostatic interactions between TLR2 and PorB surface exposed loops.

The Gonococcal Transcriptome during Infection of the Lower Genital Tract in Women.

Gonorrhea is a highly prevalent disease resulting in significant morbidity worldwide, with an estimated 106 cases reported annually. Neisseria gonorrhoeae, the causative agent of gonorrhea, colonizes and infects the human genital tract and often evades host immune mechanisms until successful antibiotic treatment is used. The alarming increase in antibiotic-resistant strains of N.

Neisseria gonorrhoeae Modulates Cell Death in Human Endocervical Epithelial Cells through Export of Exosome-Associated cIAP2.

Several bacterial pathogens persist and survive in the host by modulating host cell death pathways. We previously demonstrated that Neisseria gonorrhoeae, a Gram-negative pathogen responsible for the sexually transmitted infection gonorrhea, protects against exogenous induction of apoptosis in human cervical epithelial cells. However, induction of cell death by N.

One-step purification and porin transport activity of the major outer membrane proteins P2 from Haemophilus influenzae, FomA from Fusobacterium nucleatum and PorB from Neisseria meningitidis.

Bacterial porins are major outer membrane proteins that function as essential solute transporters between the bacteria and the extracellular environment. Structural features of porins are also recognized by eukaryotic cell receptors involved in innate and adaptive immunity. To better investigate the function of porins, proper refolding is necessary following purification from inclusion bodies [1, 2].

TLR-Dependent Human Mucosal Epithelial Cell Responses to Microbial Pathogens.

Toll-like receptor (TLR) signaling represents one of the best studied pathways to implement defense mechanisms against invading microbes in human being as well as in animals. TLRs respond to specific microbial ligands and to danger signals produced by the host during infection, and initiate downstream cascades that activate both innate and adaptive immunity. TLRs are expressed by professional immune cells and by the large majority of non-hematopoietic cells, including epithelial cells.

Immune Adjuvant Effect of Molecularly-defined Toll-Like Receptor Ligands.

Vaccine efficacy is optimized by addition of immune adjuvants. However, although adjuvants have been used for over a century, to date, only few adjuvants are approved for human use, mostly aimed at improving vaccine efficacy and antigen-specific protective antibody production. The mechanism of action of immune adjuvants is diverse, depending on their chemical and molecular nature, ranging from non-specific effects (i.

Crystallographic analysis of Neisseria meningitidis PorB extracellular loops potentially implicated in TLR2 recognition.

Among all Neisseriae species, Neisseria meningitidis and Neisseria gonorrhoeae are the only human pathogens, causative agents of bacterial meningitis and gonorrhoea, respectively. PorB, a pan-Neisseriae trimeric porin that mediates diffusive transport of essential molecules across the bacterial outer membrane, is also known to activate host innate immunity via Toll-like receptor 2 (TLR2)-mediated signaling. The molecular mechanism of PorB binding to TLR2 is not known, but it has been hypothesized that electrostatic interactions contribute to ligand/receptor binding.

In vivo and in vitro characterization of the immune stimulating activity of the Neisserial porin PorB.

Vaccines play a vital role in modern medicine. The development of novel vaccines for emerging and resistant pathogens has been aided in recent years by the use of novel adjuvants in subunit vaccines. A deeper understanding of the molecular pathways behind adjuvanticity is required to better select immunostimulatory molecules for use in individual vaccines.

Vaccination with major outer membrane protein proteosomes elicits protection in mice against a Chlamydia respiratory challenge.

Vaccines formulated with the Chlamydia muridarum native major outer membrane protein (nMOMP) have so far been shown to elicit the most robust protection against this pathogen. nMOMP is a membrane protein and therefore, detergents are used to keep it in solution. Detergents however, have toxic effects.

A mass-tagging approach for enhanced sensitivity of dynamic cytokine detection using a label-free biosensor.

Monitoring cytokine release by cells allows the investigation of cellular response to specific external stimuli, such as pathogens or candidate drugs. Unlike conventional colorimetric techniques, label-free detection of cytokines enables studying cellular secretions in real time by eliminating additional wash and labeling steps after the binding step. However, label-free techniques that are based on measuring mass accumulation on a sensor surface are challenging for measuring small cytokines binding to much larger capture agents (usually antibodies) because the relative signal change is small.

Macrophage-specific TLR2 signaling mediates pathogen-induced TNF-dependent inflammatory oral bone loss.

Porphyromonas gingivalis is a primary etiological agent of chronic periodontal disease, an infection-driven chronic inflammatory disease that leads to the resorption of tooth-supporting alveolar bone. We previously reported that TLR2 is required for P. gingivalis-induced alveolar bone loss in vivo, and our in vitro work implicated TNF as a key downstream mediator.

Toll-like receptor 2-dependent activity of native major outer membrane protein proteosomes of Chlamydia trachomatis.

Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen and the etiologic agent of blinding trachoma. Intracellular signaling pathways leading to host cell inflammation and innate immunity to Chlamydia include those mediated by Toll-like receptors (TLRs) and nucleotide binding oligomerization domain 1 (Nod1) protein. In epithelial cells, TLR-dependent signaling contributes to local immune responses via induction of inflammatory mediators.