Immunological Memory Transferred with CD4 T Cells Specific for Tuberculosis Antigens Ag85B-TB10.4: Persisting Antigen Enhances Protection

BACKGROUND:High levels of death and morbidity worldwide caused by tuberculosis has stimulated efforts to develop a new vaccine to replace BCG. A number of Mycobacterium tuberculosis (Mtb)-specific antigens have been synthesised as recombinant subunit vaccines for clinical evaluation. Recently a fusion protein of TB antigen Ag85B combined with a second immunodominant TB antigen TB10.4 was emulsified with a novel non-phospholipid-based liposomal adjuvant to produce a new subunit vaccine, investigated here. Currently, there is no consensus as to whether or not long-term T cell memory depends on a source of persisting antigen. To explore this and questions regarding lifespan, phenotype and cytokine patterns of CD4 memory T cells, we developed an animal model in which vaccine-induced CD4 memory T cells could transfer immunity to irradiated recipients. METHODOLOGY/PRINCIPAL FINDINGS:The transfer of protective immunity using Ag85B-TB10.4-specific, CD45RB(low) CD62L(low) CD4 T cells was assessed in sub-lethally irradiated recipients following challenge with live BCG, used here as a surrogate for virulent Mtb. Donor T cells also carried an allotype marker allowing us to monitor numbers of antigen-specific, cytokine-producing CD4 T cells in recipients. The results showed that both Ag85B-TB10.4 and BCG vaccination induced immunity that could be transferred with a single injection of 3x10(6) CD4 T cells. Ten times fewer numbers of CD4 T cells (0.3x10(6)) from donors immunised with Ag85B-TB10.4 vaccine alone, transferred equivalent protection. CD4 T cells from donors primed by BCG and boosted with the vaccine similarly transferred protective immunity. When BCG challenge was delayed for 1 or 2 months after transfer (a test of memory T cell survival) recipients remained protected. Importantly, recipients that contained persisting antigen, either live BCG or inert vaccine, showed significantly higher levels of protection (p<0.01). Overall the numbers of IFN-gamma-producing CD4 T cells were poorly correlated with levels of protection. CONCLUSIONS/SIGNIFICANCE:The Ag85B-TB10.4 vaccine, with or without BCG-priming, generated TB-specific CD4 T cells that transferred protective immunity in mice challenged with BCG. The level of protection was enhanced in recipients containing a residual source of specific antigen that could be either viable or inert

The effect of color type on early wound healing in farmed mink (Neovison vison)

Abstract Background Individual differences of mink, including color type, are speculated to affect the course of wound healing, thereby impacting wound assessment and management on the farms, as well as the assessment of wounds in forensic cases. In this study, we examined the effect of color type on early wound healing in farmed mink. Full thickness excisional wounds (2 × 2 cm) were made on the back in 18 mink of the color types Brown, Silverblue and Blue Iris. Gross and microscopic pathology of the wounds was evaluated 2 days post-wounding together with degree of wound size reduction, presence of bacteria and blood analyses. Results Pathological examination on day 2 showed the greatest mean wound size reduction in Brown mink (11.0%) followed by Blue Iris (7.9%) and Silverblue (1.6%). Bacteria were cultured from all wounds, and predominantly Staphylococcus species were recovered in mixed or pure culture. Histopathology from day 2 wounds showed a scab overlying necrotic wound edges, which were separated from underlying vital tissue by a demarcation zone rich in polymorphonuclear leukocytes. Fibroblasts and plump endothelial cells were more numerous in the deeper tissues. Complete blood count parameters were within normal ranges in most cases, however, the mink showed mildly to markedly decreased hematocrit and six mink of the color types Silverblue and Blue Iris showed moderately elevated numbers of circulating segmented neutrophils on day 2. There was a marked increase in concentration of serum amyloid A from day 0 to day 2 in all color types. Conclusions We have described differences in early wound healing between mink of the color types Brown, Silverblue and Blue Iris by use of an experimental wound model in farmed mink. The most pronounced difference pertained to the degree of wound size reduction which was greatest in Brown mink, followed by Blue Iris and Silverblue, respectively

Mid-infrared supercontinuum generation to 12.5μm in large NA chalcogenide step-index fibres pumped at 4.5μm

We present numerical modeling of mid-infrared (MIR) supercontinuum generation (SCG) in dispersion-optimized chalcogenide (CHALC) step-index fibres (SIFs) with exceptionally high numerical aperture (NA) around one, pumped with mode-locked praseodymium-doped (Pr3+) chalcogenide fibre lasers. The 4.5um laser is assumed to have a repetition rate of 4MHz with 50ps long pulses having a peak power of 4.7kW. A thorough fibre design optimisation was conducted using measured material dispersion (As-Se/Ge-As-Se) and measured fibre loss obtained in fabricated fibre of the same materials. The loss was below 2.5dB/m in the 3.3-9.4μm region. Fibres with 8 and 10μm core diameters generated an SC out to 12.5 and 10.7μm in less than 2m of fibre when pumped with 0.75 and 1kW, respectively. Larger core fibres with 20μm core diameters for potential higher power handling generated an SC out to 10.6μm for the highest NA considered but required pumping at 4.7kW as well as up to 3m of fibre to compensate for the lower nonlinearities. The amount of power converted into the 8-10μm band was 7.5 and 8.8mW for the 8 and 10μm fibres, respectively. For the 20μm core fibres up to 46mW was converted. © 2014 Optical Society of America

Prevalence of Coxielle Burnetii anbitodies in Danish Dairy herds

<p>Abstract</p> <p>During recent years in Denmark higher rates of antibodies to <it>Coxiella burnetii </it>have been detected in animals and humans than previously reported. A study based on bulk tank milk samples from 100 randomly selected dairy herds was performed to estimate the prevalence and geographical distribution of antibody positive dairy herds. Using the CHEKIT Q-Fever Antibody ELISA Test Kit (IDEXX), the study demonstrated a prevalence of 59% antibody positive herds, 11% antibody intermediate herds and 30% antibody negative herds based on the instructions provided by the manufacturer. The geographical distribution does not indicate a relationship between the regional density of dairy farms and the prevalence of antibody positive dairy farms. The result supports the hypothesis of an increase in the prevalence of positive dairy herds compared to previous years.</p

A Liposome-Based Mycobacterial Vaccine Induces Potent Adult and Neonatal Multifunctional T Cells through the Exquisite Targeting of Dendritic Cells

BACKGROUND: In the search for more potent and safer tuberculosis vaccines, CAF01 was identified as a remarkable formulation. Based on cationic liposomes and including a synthetic mycobacterial glycolipid as TLR-independent immunomodulator, it induces strong and protective T helper-1 and T helper-17 adult murine responses to Ag85B-ESAT-6, a major mycobacterial fusion protein. Here, we assessed whether these properties extend to early life and how CAF01 mediates its adjuvant properties in vivo. METHODS/FINDINGS: Following adult or neonatal murine immunization, Ag85B-ESAT-6/CAF01 similarly reduced the post-challenge bacterial growth of M. bovis BCG, whereas no protection was observed using Alum as control. This protection was mediated by the induction of similarly strong Th1 and Th17 responses in both age groups. Multifunctional Th1 cells were already elicited after a single vaccine dose and persisted at high levels for at least 6 months even after neonatal priming. Unexpectedly, this potent adjuvanticity was not mediated by a massive targeting/activation of dendritic cells: in contrast, very few DCs in the draining lymph nodes were bearing the labeled antigen/adjuvant. The increased expression of the CD40 and CD86 activation markers was restricted to the minute portion of adjuvant-bearing DCs. However, vaccine-associated activated DCs were recovered several days after immunization. CONCLUSION: The potent adult and neonatal adjuvanticity of CAF01 is associated in vivo with an exquisite but prolonged DC uptake and activation, fulfilling the preclinical requirements for novel tuberculosis vaccines to be used in early life

(Re)Storying Obama: An Examination of Recently Published Informational Texts

American publishers have published numerous children’s books about Barack Obama over the past several years; most take the form of informational biographies. This article reports on a research project aimed at how these books incorporate sociohistorical narratives, particularly those related to the civil rights movement. Though the features of the books might cause the reader to presume political neutrality, the books link readers to distinct Discourses (Gee, 1996), suggesting particular ideologies. In this article, we identified the following differences: (1) specific happenings from Obama’s life were included in some texts while omitted in others; (2) when the events were included, how they were framed differed; and (3) the narrative constructions of the events varied. We use the differences amongst these texts to argue for the importance of critical literacy in elementary classrooms

Occupational Therapy Intervention with Children Survivors of War

A preventive occupational therapy program with children surviving the Kosovo conflict is examined. The objective of the program was to facilitate the emotional expression of traumatic experiences in order to prevent the development of future psychological problems. The intervention was based on a community-centred approach with spirituality as a central focus of the intervention.The Model of Human Occupation and the Occupational Performance Process Model were utilized to guide the identification and intervention of occupational performance issues.The children’s return from a land of war to a land of children demonstrates the potential of occupational therapy intervention in this field. With increasing awareness of populations facing social and political challenges, there is a growing importance of the concept of occupational justice and the need to work against occupational apartheid.Cet article décrit un programme de prévention en ergothérapie qui était destiné aux enfants ayant survécu au conflit du Kosovo. L’objectif du programme était d’aider les enfants à exprimer les émotions qu’ils avaient ressenties lors d’expériences traumatiques afin de prévenir l’apparition de problèmes psychologiques. L’intervention était basée sur une approche communautaire s’articulant autour de la spiritualité. Le Modèle de l’occupation humaine et le Modèle du processus d’intervention dans le rendement occupationnel ont été utilisés pour cibler les difficultés en matière de rendement occupationnel et pour déterminer les interventions requises. Le retour des enfants d’un monde de guerre vers le monde de l’enfance démontre la possibilité de proposer une intervention ergothérapique dans ce domaine. La conscientisation de plus en plus grand face à la détresse des populations confrontées à des problèmes politiques et sociaux entraîne une augmentation de l’importance du concept de la justice occupationnelle et du besoin de lutter contre l’apartheid occupationnel

Cluster of Sylvatic Epidemic Typhus Cases Associated with Flying Squirrels, 2004–2006

Infected persons had slept in an infested cabin