Immunogenicity of a single dose of reduced-antigen acellular pertussis vaccine in a non-vaccinated adolescent population.

Abstract German adolescents ( n  = 123) without previous pertussis vaccination, no history of pertussis and low IgG-anti-pertussis-toxin (PT) levels received one dose of the Tdap vaccine Boostrix™. Blood samples were taken before, and 5–12 days and 29–49 days after vaccination. IgG- and IgA-anti-PT, IgG- and IgA-anti filamentous hemagglutinin, IgG-anti-pertactin, IgG-anti-tetanus-toxin, and IgG-anti-diphtheria-toxin were measured by ELISA. 88.6% of subjects had an immune response to PT, and all vaccinees had an immune response to at least one pertussis antigen 29–49 days after vaccination. IgA-anti-PT and IgA-anti-FHA responses were found in 43 and 81% of subjects, respectively. This study …

Monophosphoryl lipid A coating of hydroxyethyl starch nanocapsules drastically increases uptake and maturation by dendritic cells while minimizing the adjuvant dosage.

Enhancing delivery of antigens to dendritic cells (DCs) is essential for the induction of vigorous antigen-specific cellular immune responses. Aim of the present study was to evaluate the properties of hydroxyethyl starch nanocapsules (HES-NCs) functionalized with anti-CD40, anti-DEC205, interferon-γ (IFNγ) and/or monophosphoryl lipid A (MPLA) with respect to the overall uptake, the released cytokine profile, and the influence on phenotypic maturation of human monocyte-derived DCs using flow cytometry, confocal microscopy and enzyme-linked immunosorbent assays. NC uptake by DCs was significantly enhanced by functionalizing NCs with anti-CD40 or MPLA. With respect to the cytokine profile and…

Booster vaccination after neonatal priming with acellular pertussis vaccine.

After a birth dose of acellular pertussis (aP) and diphtheria (DT)aP-hepatitis B virus (HBV)-inactivated polio vaccine (IPV)/ Haemophilus influenza type b (Hib) at 2, 4, and 6 months, a booster dose of DTaP-HBV-IPV/Hib at 12 to 23 months induced strong anti-pertussis booster responses. Thus, neonatal aP priming did not lead to immune tolerance to pertussis antigens. However, it elicited bystander interference on HBV, Hib, and diphtheria responses.

In the presence of IL-21 human cord blood T cells differentiate to IL-10-producing Th1 but not Th17 or Th2 cells.

Abstract IL-21, a member of the IL-2 cytokine family, is mainly produced by activated CD4+ T cells and controls the activity of immune and also non-immune cells. As a pleiotropic cytokine, IL-21 acts on both innate and adaptive immune responses, suggesting that IL-21 may be a master regulator of the T-cell-dependent adaptive immune response. Although IL-21 is described as mostly promoting inflammation, evidence also suggests inhibitory effects of IL-21. However, its role, particularly in the human neonatal immune system, has not been detailed so far. Here, we assessed the effect of IL-21 in the specific context of the neonatal immune response and delineated differences between the human new…

The influence of major histocompatibility complex class II genes and T-cell Vbeta repertoire on response to immunization with HBsAg.

Nonresponsiveness to HBsAg vaccination is observed in 5-10% of vaccine recipients and is possibly caused by a defect in the T helper cell compartment. The immune response to HBsAg is influenced by genes of the major histocompatibility complex. We have investigated MHC class I and class II antigens in 53 adult responders and 73 nonresponders. Results obtained in this first study were tested in a second study with 56 responders and 62 nonresponders from an infant vaccination trial. In addition, the peripheral Vbeta-chain T-cell receptor repertoire was investigated using monoclonal antibodies and flow-cytometry in 26 adult responders and 38 nonresponders. As previously reported, nonresponsiven…

IL-27 improves migrational and antiviral potential of CB dendritic cells.

Abstract Interleukin (IL)-27 is known to be increased considerably in cord blood (CB) dendritic cells (DCs) after TLR ligation. Previously, we demonstrated that also basal IL-27 levels are higher in CB DCs. Here, we examined effects of IL-27 on monocyte derived dendritic cells (moDCs) to approach its particular role in the specialized immune system of the human neonate. Exogenous IL-27 promotes IL-27 transcription in CB and adult blood (AB) moDCs. IL-27 acts on CB moDCs primarily by significantly augmenting IL-27 protein, secondarily by increasing transcription of CXCL10 among other chemokines, chemokine receptor CCR1, interferon stimulated genes, transcription factor IRF8 and genes involve…

Instruction of haematopoietic lineage choices, evolution of transcriptional landscapes and cancer stem cell hierarchies derived from an AML1-ETO mouse model.

The t(8;21) chromosomal translocation activates aberrant expression of the AML1-ETO (AE) fusion protein and is commonly associated with core binding factor acute myeloid leukaemia (CBF AML). Combining a conditional mouse model that closely resembles the slow evolution and the mosaic AE expression pattern of human t(8;21) CBF AML with global transcriptome sequencing, we find that disease progression was characterized by two principal pathogenic mechanisms. Initially, AE expression modified the lineage potential of haematopoietic stem cells (HSCs), resulting in the selective expansion of the myeloid compartment at the expense of normal erythro- and lymphopoiesis. This lineage skewing was foll…

Cordycepin is an immunoregulatory active ingredient of Cordyceps sinensis.

We have reported that cordycepin, an adenosine derivative from the fungus Cordyceps, increased interleukin (IL)-10 expression, decreased IL-2 expression and suppressed T lymphocyte activity. In the present study, we further characterized the regulatory effects of cordycepin on human immune cells. Moreover, a traditional Chinese drug, Cordyceps sinensis (CS) that contains cordycepin, was also investigated. Cytometric Bead Array (CBA) was used to determine the concentrations of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-alpha and IFN-gamma in culture of peripheral blood mononuclear cells (PBMCs). The results showed that both cordycepin and CS up-regulated IL-10, IL-1beta, IL-6,…

The non-neuronal cholinergic system in peripheral blood cells: Effects of nicotinic and muscarinic receptor antagonists on phagocytosis, respiratory burst and migration

Peripheral blood cells express the complete non-neuronal cholinergic system. For example synthesis of acetylcholine and nicotinic as well muscarinic receptors have been demonstrated in leucocytes isolated from human peripheral blood. In the present experiments mononuclear cells and granulocytes were isolated from the peripheral blood to investigate content and synthesis of acetylcholine as well as phenotypic functions like respiratory burst, phagocytosis and migration. Mononuclear cells (T-cells and monocytes) contained 0.36 pmol/10(6) cells acetylcholine, whereas acetylcholine content in granulocytes was 100-fold lower. Acetylcholine synthesis amounted to 23.2+/-4.7 nmol/mg protein/h and 2…

Tubulin gene expression persists during all changes in microtubular arrays related to cell shaping in growing barley leaves

Summary Levels of α-tubulin RNA were determined in consecutive leaf segments taken along young, growing barley leaves by Northern blotting. The leaves exhibited a developmental gradient typical of graminaceous species ranging from a meristem at the base to fully differentiated cells at the tip. The objective was to ascertain whether or not high steady-state tubulin RNA levels accompany characteristic changes in microtubular arrays known to occur during cell division and differentiation. Of particular interest was the differentiation zone comprising a succession of well defined changes in microtubular arrays that appear to be involved in the control of cell shaping. High steady-state levels …

Inflammatory Characteristics of Monocytes from Pediatric Patients with Tuberous Sclerosis.

Objective  Therapeutic options for the tuberous sclerosis complex (TSC) syndrome showed varying outcomes. Malfunctional tsc1 / tsc2 genes leave mTOR uninhibited, a positive downstream modulator of the innate proinflammatory immune system, which has not yet been described in pediatric patients with TSC. Methods  Using polymerase chain reaction (PCR) gene expression levels of monocytes after cultivation with lipopolysaccharide (LPS) or with LPS + mTOR inhibitor rapamycin, patients with TSC ( n  = 16) were compared with healthy subjects ( n  = 20). Results  Compared with monocytes from healthy controls, LPS showed a more prominent gene expression pattern in patients with TSC (CCL24, CXCL10, IL…

Gut microbiota differs between children with Inflammatory Bowel Disease and healthy siblings in taxonomic and functional composition: a metagenomic analysis.

Current treatment for pediatric inflammatory bowel disease (IBD) patients is often ineffective, with serious side effects. Manipulating the gut microbiota via fecal microbiota transplantation (FMT) is an emerging treatment approach but remains controversial. We aimed to assess the composition of the fecal microbiome through a comparison of pediatric IBD patients to their healthy siblings, evaluating risks and prospects for FMT in this setting. A case-control (sibling) study was conducted analyzing fecal samples of six children with Crohn’s disease (CD), six children with ulcerative colitis (UC) and 12 healthy siblings by metagenomic sequencing. In addition, lifetime antibiotic intake was r…

Zur Pathologie und Klinik der h�morrhagischen und nekrotisierenden S�uglingsenteritis durch Escherichia coli O 127?B 8

Klinischer Verlauf und pathologisch-anatomische Befunde von 25 Sauglingen im 1. Trimenon, die im Verlauf einer Enteritisepidemie durch Escherichia coli O 127: B 8 verstorben waren, werden ausfuhrlich dargestellt. Es werden epidemiologische Fragen erortert und klinisch ein perakuter Krankheitsverlauf bei Fruhgeborenen und eine protrahierte Form bei alteren Kindern unterschieden. Morphologisch bestand eine ungewohnlich schwere bamorrhagische und nekrotisierende Enteritis mit Geschwurbildung. Die Enteritis hatte bei den Sauglingen der jungeren Altersgruppe den gesamten Verdauungskanal von Oesophagus bis Rectum befallen, bei alteren Kindern blieb die Enteritis auf Dunndarm und Colonteile beschr…

Safety and reactogenicity of a novel DTPa-HBV-IPV combined vaccine given along with commercial Hib vaccines in comparison with separate concomitant administration of DTPa, Hib, and OPV vaccines in infants.

Objective. Combination vaccines simplify vaccine administration and have the potential to promote compliance and cost-effectiveness by decreasing the number of injections needed to immunize a child. The objective of this study was to assess the safety and reactogenicity of the diphtheria-tetanus toxoid-acellular pertussis-hepatitis B virus-inactivated polio virus (DTPa-HBV-IPV) vaccine when coadministered with different Haemophilus influenzae type B (Hib) vaccines in comparison with separate, commercially available, control vaccines in a 3-dose primary vaccination series. Methods. An open-label, randomized, parallel-group study in 5318 infants who were 8 to 16 weeks of age at enrollment was…

Human toll-like receptor 4 mutations are associated with susceptibility to invasive meningococcal disease in infancy.

Toll-like receptor 4 (TLR4) is required for efficient recognition of bacterial infections. We investigated an association between 2 TLR4 mutations (Asp 299 Gly and Thr 399 Ile) and meningococcal disease in 197 patients and 214 healthy controls by allele-specific real time polymerase chain reaction and direct sequencing. Although the allele frequency was not higher in the overall patient population, a significantly higher frequency in the 40 patients younger than 12 months of age (P = 0.007) was observed. We conclude that TLR4 mutations represent a risk factor for meningococcal disease in this age group.

Age-Dependent Association of Human Mannose-Binding Lectin Mutations With Susceptibility to Invasive Meningococcal Disease in Childhood

Mannose-binding lectin (MBL) is an important factor of the innate immune system, and MBL-initiated complement activation is an important early defense mechanism against various bacterial infections, including invasive meningococcal disease.In a pediatric cohort (ages 2-215 months) with invasive meningococcal disease, we investigated the overall and age-stratified frequency of 3 MBL exon 1 variations (C154T, G161A, G170A), previously shown to result in markedly decreased MBL plasma concentrations, by allele specific fluorescent hybridization probe real-time PCR assays and direct sequencing. Healthy age-matched volunteers with the same ethnic background and no history of meningococcal disease…

Enhanced in vivo targeting of murine nonparenchymal liver cells with monophosphoryl lipid A functionalized microcapsules.

A broad spectrum of infectious liver diseases emphasizes the need of microparticles for targeted delivery of immunomodulatory substances to the liver. Microcapsules (MCs) are particularly attractive for innovative drug and vaccine formulations, enabling the combination of antigen, drugs, and adjuvants. The present study aimed to develop microcapsules characterized by an enhanced liver deposition and accelerated uptake by nonparenchymal liver cells (NPCs). Initially, two formulations of biodegradable microcapsules were synthesized from either hydroxyethyl starch (HES) or mannose. Notably, HES-MCs accumulated primarily in the liver, while mannose particles displayed a lung preference. Functio…

Cellular Immunity in Adolescents and Adults following Acellular Pertussis Vaccine Administration

ABSTRACT Cell-mediated immune (CMI) responses to an acellular pertussis vaccine administered to 49 subjects, a subset of participants in the National Institutes of Health-funded adult acellular pertussis vaccine efficacy trial, were evaluated and compared with antibody responses to vaccine antigens. Levels of proliferation of and cytokine secretion from lymphocytes cultured in the presence of pertussis toxin, filamentous hemagglutinin, or pertactin were measured before vaccination and 1 month and 1 year after vaccination. Statistically significant increases in lymphocyte stimulation indices and cytokine secretion were noted at both 1 month and 1 year after vaccination. Brisk pertussis antig…

Immunogenicity and reactogenicity of HbOC vaccine administered simultaneously with acellular pertussis vaccine (DTaP) into either arms or thighs of infants.

To evaluate the reactogenicity and immunogenicity of a Haemophilus influenzae type b conjugate vaccine (HbOC) and of a tricomponent acellular pertussis vaccine (DTaP) when injected simultaneously into either contralateral arms or into contralateral thighs, 110 infants were enrolled to receive three doses of DTaP at 3, 4, and 5 months and two HbOC doses at 3 and 5 months of age. Administration of either of the two vaccines into arms was associated with significantly more local side effects than administration into thighs. There was no difference in geometric mean concentration (GMC) values for any of the four vaccine antigens between subjects who had been vaccinated into arms or thighs. Afte…

Immunogenicity and reactogenicity of acellular pertussis booster vaccines in children: standard pediatric versus a reduced-antigen content formulation.

Booster vaccination with a reduced-antigen-content dTpa, pediatric DTPa or adult Td vaccine in DTPa-primed children aged 4-6 years was evaluated. Immunogenicity and CMI was assessed one month and 3.5 years after vaccination. Symptoms were solicited for 15 days post-vaccination. There were no differences between groups in diphtheria or tetanus seroprotection or pertussis vaccine-response rates. Anti-diphtheria and anti-PRN concentrations were higher after DTPa, but groups differences reduced over time. Non-significant trends toward reduced reactogenicity of dTpa were observed. Many factors influence vaccine choice at pre-school age. The dTpa vaccine was as immunogenic and possibly better tol…

Effect of cordycepin on interleukin-10 production of human peripheral blood mononuclear cells

Therapeutic options for controlling autoimmune diseases are still very limited. Interleukin-10 has been reported to be a promising approach to therapeutic intervention. In the search for a drug which results in the selective upregulation of interleukin-10, we investigated the immunoregulative effects of cordycepin. We have measured interleukin-10 and interleukin-2 secretion of human peripheral blood mononuclear cells that were incubated with cordycepin and assessed the influence of cordycepin on the expression of interleukin-10 mRNA, the proliferative response and the expression of surface markers on T lymphocytes. In addition, the subsets of interleukin-10-secreting cells, the influence of…

Comparison of intramuscular and subcutaneous administration of a herpes zoster live-attenuated vaccine in adults aged ≥50 years: a randomised non-inferiority clinical trial.

AbstractZostavax® is a live, attenuated varicella zoster virus (VZV) vaccine developed specifically for the prevention of HZ and PHN in individuals aged ≥50 years. During the clinical development of Zostavax, which was mainly in the US, the vaccine was administrated by the subcutaneous (SC) route. In Europe, many healthcare professionals prefer administering vaccines by the intramuscular (IM) route. This was an open-label, randomised trial conducted in 354 subjects aged ≥50 years. The primary objectives were to demonstrate that IM administration is both non-inferior to SC administration in terms of 4-week post-vaccination geometric mean titres (GMTs), and elicits an acceptable geometric mea…

Effects of pathogen reduction systems on platelet microRNAs, mRNAs, activation, and function

Pathogen reduction (PR) systems for platelets, based on chemically induced cross-linking and inactivation of nucleic acids, potentially prevent transfusion transmission of infectious agents, but can increase clinically significant bleeding in some clinical studies. Here, we documented the effects of PR systems on microRNA and mRNA levels of platelets stored in the blood bank, and assessed their impact on platelet activation and function. Unlike platelets subjected to gamma irradiation or stored in additive solution, platelets treated with Intercept (amotosalen + ultraviolet-A [UVA] light) exhibited significantly reduced levels of 6 of the 11 microRNAs, and 2 of the 3 anti-apoptotic mRNAs (B…

Laminar Implantation of a Collagen-Elastin Matrix Improves Infraorbital Contour in Aesthetic Facial Surgery