TLR agonist combinations that stimulate Th type I polarizing responses from human neonates.

Each year millions of neonates die due to vaccine preventable infectious diseases. Our study seeks to develop novel neonatal vaccines and improve immunogenicity of early childhood vaccines by incorporating TLR agonist-adjuvant combinations that overcome the inherent neonatal Th2 bias and stimulate Th1 polarizing response from neonatal APCs. We systematically stimulated cord blood mononuclear cells with single and multiple combinations of TLR agonists and measured levels of IL-12p70, IFN-γ, IFN-α, IL-10, IL-13, TNF-α, IL-6 and IL-1β from cell culture supernatants.

Epigenetic impacts of stress priming of the neuroinflammatory response to sarin surrogate in mice: a model of Gulf War illness.

Background: Gulf War illness (GWI) is an archetypal, medically unexplained, chronic condition characterised by persistent sickness behaviour and neuroimmune and neuroinflammatory components. An estimated 25-32% of the over 900,000 veterans of the 1991 Gulf War fulfil the requirements of a GWI diagnosis. It has been hypothesised that the high physical and psychological stress of combat may have increased vulnerability to irreversible acetylcholinesterase (AChE) inhibitors leading to a priming of the neuroimmune system.

Haemophilus influenzae-protein D specific antibody correlate with protection against acute otitis media in young children.

Background: Haemophilus influenzae (Hi) causes respiratory infections and pathogenesis of this microbe begins in the human nasopharynx (NP). The objective of this study was to assess the correlation of NP colonization-induced serum antibody levels to Hi protein D with risk of acute otitis media (AOM) in children <2 yr.

Methods: 455 sera from 213 children (age 6-24 months old) were collected when they were colonized with Hi and when the children developed AOM.

Three Innate Cytokine Biomarkers Predict Presence of Acute Otitis Media and Relevant Otopathogens.

Background: 1.1Diagnosis of Acute Otitis Media (AOM) is challenging, resulting in frequent over diagnosis and improper prescription of antibiotics. A serum biomarker of AOM would significantly improve pediatric care for this common illness.

PKK deletion in basal keratinocytes promotes tumorigenesis after chemical carcinogenesis.

Squamous cell carcinoma (SCC) of the skin is a keratinocyte malignancy characterized by tumors presenting on sun-exposed areas with surgery being the mainstay treatment. Despite advances in targeted therapy in other skin cancers, such as basal cell carcinoma and melanoma, there have been no such advances in the treatment of SCC. This is partly due to an incomplete knowledge of the pathogenesis of SCC.

Pneumococcal whole-cell and protein-based vaccines: changing the paradigm.

Epidemiologic evaluations of Streptococcus pneumoniae nasopharyngeal (NP) colonization and pneumococcal disease suggest that newer serotypes in future formulations of pneumococcal conjugate vaccines (PCVs) are needed and there may need to be continued reformulations because there are many new emerging serotypes expressed by pneumococci. Areas covered: Mechanisms of protection by next-generation whole-cell vaccine (WCV) and/or multi-component pneumococcal purified protein vaccines (PPVs) in development for prevention of pneumococcal infections. Expert commentary: A long-term strategy for prevention of pneumococcal disease will likely include WCV and PPVs.

Streptococcus pneumoniae burden and nasopharyngeal inflammation during acute otitis media.

Streptococcus pneumoniae (Spn) is a common respiratory pathogen and a frequent cause of acute otitis media (AOM) in children. The first step in bacterial pathogenesis of AOM is the establishment of asymptomatic colonization in the nasopharynx. We studied Spn bacterial burden in conjunction with neutrophil recruitment and inflammatory gene transcription and cytokine secretion in samples of nasal wash collected from normal and otitis-prone children during health, viral upper respiratory infection without middle ear involvement (URI) and AOM.

Chronic social stress Ameliorates psoriasiform dermatitis through upregulation of the Hypothalamic-Pituitary-Adrenal axis.

Acute stress is a physiological response of an organism to adverse conditions, contributing to survival; however, persistence through time may lead to disease. Indeed, exacerbation of inflammatory conditions such as psoriasis has been reported to follow stressors in susceptible patients. Because chronic stress cannot ethically be elicited in patients under controlled laboratory conditions, we studied genetically modified mice that naturally develop psoriasiform dermatitis, and subjected them to an ethological chronic social contact stress paradigm.

Comparison of direct-plating and broth-enrichment culture methods for detection of potential bacterial pathogens in respiratory secretions.

Objective: We compared the recovery of potential respiratory bacterial pathogens and normal flora from nasopharyngeal specimens collected from children during health and at the onset of acute otitis media (AOM) by selective direct-plating and overnight broth-enrichment.

Methods: Overall, 3442 nasal wash (NW) samples collected from young children were analysed from a 10-year prospective study. NWs were cultured by (1) direct-plating to TSAII/5 % sheep blood agar and chocolate agar plates and (2) overnight broth-enrichment in BacT/ALERT SA-broth followed by plating.

Cross-reactivity in β-Lactam Allergy.

β-Lactam drugs (penicillins, amoxicillin, and cephalosporins) account for 42.6% of all severe drug-induced anaphylaxis. In this review, we focus on clinically significant immunologic cross-reactivity in patients with confirmed penicillin allergy to cephalosporins, and the structural involvement of the R and R chemical side chains of the cephalosporins causing IgE-mediated cross-reactivity with penicillin and other cephalosporins.

Decreased TNF family receptor expression on B-cells is associated with reduced humoral responses to Streptococcus pneumoniae infections in young children.

An underdeveloped or impaired immune response in young children is associated with increased susceptibility to Streptococcus pneumonia (Spn) infections. We determined serum antibody titers against 3 Spn vaccine candidate proteins and vaccine serotype polysaccharide antigens in a group of Spn infection prone 9-18months old and found lower IgG antibody titers to all tested antigens compared to age-matched non-infection-prone children. We also found the children had significantly reduced percentages of total memory B-cells, switched memory B-cells and plasma cells.

Modeling specific antibody responses to natural immunization to predict a correlate of protection against infection before commencing a clinical vaccine trial.

Background: Clinical trials of vaccines for children to prevent acute otitis media (AOM) infections caused by the bacteria Streptococcus pneumonia (Spn) are in Phase I. The objective of this study was to use serum antibody measurements to pneumococcal purified protein candidate antigens that occurred after natural "immunization" to predict a correlate of protection response needed following an injectable vaccine against AOM in children.

Methods: 590 nasal and serum samples were collected from 129 healthy children at 6, 9, 12, 15, 18, 24 and 30-36 months of age and when the child developed AOM.

Stringently Defined Otitis Prone Children Demonstrate Deficient Naturally Induced Mucosal Antibody Response to Proteins.

() is a prominent mucosal pathogen causing acute otitis media (AOM). We studied nasopharyngeal (NP) colonization, AOM frequency and mucosal antibody responses to four vaccine candidate proteins: outer membrane protein (OMP) CD, oligopeptide permease (Opp) A, hemagglutinin (Hag), and Pilin A clade 2 (PilA2) from stringently defined otitis prone (sOP) children, who experience the greatest burden of disease, compared to non-otitis prone (NOP) children. sOP children had higher NP colonization of (30 vs.

Evaluation of the Relationship between Alopecia Areata and Viral Antigen Exposure.

Background: Alopecia areata (AA) is an autoimmune disease characterized by non-scarring alopecia with T-cell infiltration at the affected hair follicle.

Objective: Our aim was to study the potential link between hepatitis B virus (HBV) antigen exposure and AA.

Methods: Two pediatric patients with AA following hepatitis B vaccination were identified in a general dermatology clinic.

Epidemiology of Acute Otitis Media in the Postpneumococcal Conjugate Vaccine Era.

Objectives: To study the epidemiology of acute otitis media (AOM), especially the otitis-prone condition, during the pneumococcal conjugate vaccines 7 and 13 era.

Methods: Six hundred and fifteen children were prospectively managed from 6 to 36 months of life during a 10-year time frame (June 2006-June 2016). All clinical diagnoses of AOM were confirmed by tympanocentesis and bacterial culture of middle ear fluid.

Serum antibody response to Moraxella catarrhalis proteins in stringently defined otitis prone children.

Background: Moraxella catarrhalis (Mcat) is a frequent pathogen of acute otitis media (AOM) in young children. Here we prospectively assessed naturally-induced serum antibodies to four Mcat vaccine candidate proteins in stringently defined otitis prone (sOP) and non-otitis prone (NOP) children age 6-36months old following nasopharyngeal (NP) colonization, at onset of AOM and convalescence from AOM.

Methods: Serum IgG and IgM antibody against recombinant Mcat proteins, oligopeptide permease A (OppA), outer membrane protein (OMP) CD, hemagglutinin (Hag), and PilA clade 2 (PilA2), were quantitated by ELISA.

A PCR-based method for quantifying neutrophils in human nasal secretions.

Neutrophil recruitment to the nasopharynx (NP) is a central event in resolution of NP-initiated microbial infections. A vigorous neutrophil response in infected tissues is also associated with the outcome of adverse tissue pathology. Therefore, differences in infection-induced tissue neutrophil numbers may correlate with pathogenesis events.

Panel 5: Immunology.

Objective To perform a state-of-the-art review of the literature from January 2012 through May 2015 on studies that advanced our knowledge of the innate and adaptive immunology related to otitis media. This review also proposes future directions for research in this area. Data Sources PubMed database of the National Library of Medicine.

Reduced T-Helper 17 Responses to Streptococcus pneumoniae in Infection-Prone Children Can Be Rescued by Addition of Innate Cytokines.

Background: T-helper (Th) 17 cells are important in the control of Streptococcus pneumoniae. We sought to understand the mechanism of failure of Th17 immunity resulting in S. pneumoniae infections in children <2 years old.

Correlation of higher antibody levels to pneumococcal proteins with protection from pneumococcal acute otitis media but not protection from nasopharyngeal colonization in young children.

Objectives: We previously found that nasopharyngeal (NP) colonization by Streptococcus pneumoniae elicits mucosal antibody responses to three protein vaccine candidates: pneumococcal histidine triad protein D (PhtD), pneumococcal choline-binding protein A (PcpA), and detoxified pneumolysin (PlyD1). Here we sought to determine if mucosal antibody levels to the proteins correlated with protection from acute otitis media (AOM) and NP colonization.

Methods: A total of 228 NP samples were prospectively collected from 100 healthy infants at 6-24 months of age.

Differences in innate immune response gene regulation in the middle ear of children who are otitis prone and in those not otitis prone.

Objective: Acute otitis media (AOM) causes an inflammatory response in the middle ear. We assessed differences in innate immune responses involved in bacterial defense at onset of AOM in children who were stringently defined as otitis prone (sOP) and children not otitis prone (NOP).

Study Design: Innate immune genes analysis from middle ear fluid (MEF) samples of children.

Trivalent pneumococcal protein vaccine protects against experimental acute otitis media caused by Streptococcus pneumoniae in an infant murine model.

Background: Currently licensed serotype-based pneumococcal vaccines are effective in preventing invasive pneumococcal diseases, but less effective in preventing non-bacteremic pneumonia and acute otitis media (AOM). We previously reported that a trivalent pneumococcal protein recombinant vaccine (PPrV) protected against pneumonia in a murine model. Here we evaluated PPrV protection against AOM in an infant murine model.

Protection against Streptococcus pneumoniae Invasive Pathogenesis by a Protein-Based Vaccine Is Achieved by Suppression of Nasopharyngeal Bacterial Density during Influenza A Virus Coinfection.

An increase in Streptococcus pneumoniae nasopharynx (NP) colonization density during a viral coinfection initiates pathogenesis. To mimic natural S. pneumoniae pathogenesis, we commensally colonized the NPs of adult C57BL/6 mice with S.