Adjuvant-free immunization with infective filarial larvae as lymphatic homing antigen carriers

International audienceControlled infection with intestinal nematodes has therapeutic potential for preventing the symptoms of allergic and autoimmune diseases. Here, we engineered larvae of the filarial nematode Litomosoides sigmodontis as a vaccine strategy to induce adaptive immunity against a foreign, crosslinked protein, chicken egg ovalbumin (OVA), in the absence of an external adjuvant. The acylation of filarial proteins with fluorescent probes or biotin was not immediately detrimental to larval movement and survival, which died 3 to 5 days later. At least some of the labeled and skin-inoculated filariae migrated through lymphatic vessels to draining lymph nodes. The immunization potential of OVA-biotin-filariae was compared to that of an OVA-bound nanoparticulate carrier co-delivered with a CpG adjuvant in a typical vaccination scheme. Production of IFNγ and TNFα by restimulated CD4+ cells but not CD8+ confirmed the specific ability of filariae to stimulate CD4+ T cells. This alternative method of immunization exploits the intrinsic adjuvancy of the attenuated nematode carrier and has the potential to shift the vaccination immune response towards cellular immunity

Bistatic Radar Configuration for Soil Moisture Retrieval: Analysis of the Spatial Coverage

Some outcomes of a feasibility analysis of a spaceborne bistatic radar mission for soil moisture retrieval are presented in this paper. The study starts from the orbital design of the configuration suitable for soil moisture estimation identified in a previous study. This configuration is refined according to the results of an analysis of the spatial resolution. The paper focuses on the assessment of the spatial coverage i.e., on the verification that an adequate overlap between the footprints of the antennas is ensured and on the duty cycle, that is the fraction of orbital period during which the bistatic data are acquired. A non-cooperating system is considered, in which the transmitter is the C-band Advanced Synthetic Aperture Radar aboard Envisat. The best performances in terms of duty cycle are achieved if the transmitter operates in Wide Swath Mode. The higher resolution Image Swath Modes that comply with the selected configuration have a duty cycle that is never less than 12% and can exceed 21%. When Envisat operates in Wide Swath Mode, the bistatic system covers a wide latitude range across the equator, while in some of the Image Swath Modes, the bistatic measurements, collected from the same orbit, cover mid-latitude areas. In the latter case, it might be possible to achieve full coverage in an Envisat orbit repeat cycle, while, for a very large latitude range such as that covered in Wide Swath Mode, bistatic acquisitions could be obtained over about 65% of the area

Peripherally Administered Nanoparticles Target Monocytic Myeloid Cells, Secondary Lymphoid Organs and Tumors in Mice

Nanoparticles have been extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biology and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunological response. Here, we examine the cell-level biodistribution kinetics after administering ultrasmall Pluronic-stabilized poly(propylene sulfide) nanoparticles in the mouse. These nanoparticles depend on lymphatic drainage to reach the lymph nodes and blood, and then enter the spleen rather than the liver, where they interact with monocytes, macrophages and myeloid dendritic cells. They were more readily taken up into lymphatics after intradermal (i.d.) compared to intramuscular administration, leading to similar to 50% increased bioavailability in blood. When administered i.d., their distribution favored antigen-presenting cells, with especially strong targeting to myeloid cells. In tumor-bearing mice, the monocytic and the polymorphonuclear myeloid-derived suppressor cell compartments were efficiently and preferentially targeted, rendering this nanoparticulate formulation potentially useful for reversing the highly suppressive activity of these cells in the tumor stroma

Inhibition of Gastric Lipase as a Mechanism for Body Weight and Plasma Lipids Reduction in Zucker Rats Fed a Rosemary Extract Rich in Carnosic Acid

BACKGROUND: Rosemary (Rosmarinus officinalis L.) extracts (REs) exhibit hepatoprotective, anti-obesity and anti-inflammatory properties and are widely used in the food industry. REs are rich in carnosic acid (CA) and carnosol which may be responsible for some of the biological activities of REs. The aim of this study was to investigate whether inhibition of lipase activity in the gut may be a mechanism by which a RE enriched in CA (40%) modulates body weight and lipids levels in a rat model of metabolic disorders and obesity. METHODS AND PRINCIPAL FINDINGS: RE was administered for 64 days to lean (fa/+) and obese (fa/fa) female Zucker rats and body weight, food intake, feces weight and blood biochemical parameters were monitored throughout the study. Lipase activity (hydrolysis of p-nitrophenylbutyrate) was measured in the gastrointestinal tract at the end of the study and the contents of CA, carnosol and methyl carnosate were also determined. Sub-chronic administration of RE moderately reduced body weight gain in both lean and obese animals but did not affect food intake. Serum triglycerides, cholesterol and insulin levels were also markedly decreased in the lean animals supplemented with RE. Importantly, lipase activity was significantly inhibited in the stomach of the RE-supplemented animals where the highest content of intact CA and carnosol was detected. CONCLUSIONS: Our results confirm that long-term administration of RE enriched in CA moderates weight gain and improves the plasma lipids profile, primarily in the lean animals. Our data also suggest that these effects may be caused, at least in part, by a significant inhibition of gastric lipase and subsequent reduction in fat absorption

Synthetic Nanoparticles for Vaccines and Immunotherapy

The immune system plays a critical role in our health. No other component of human physiology plays a decisive role in as diverse an array of maladies, from deadly diseases with which we are all familiar to equally terrible esoteric conditions: HIV, malaria, pneumococcal and influenza infections; cancer; atherosclerosis; autoimmune diseases such as lupus, diabetes, and multiple sclerosis. The importance of understanding the function of the immune system and learning how to modulate immunity to protect against or treat disease thus cannot be overstated. Fortunately, we are entering an exciting era where the science of immunology is defining pathways for the rational manipulation of the immune system at the cellular and molecular level, and this understanding is leading to dramatic advances in the clinic that are transforming the future of medicine.1,2 These initial advances are being made primarily through biologic drugs– recombinant proteins (especially antibodies) or patient-derived cell therapies– but exciting data from preclinical studies suggest that a marriage of approaches based in biotechnology with the materials science and chemistry of nanomaterials, especially nanoparticles, could enable more effective and safer immune engineering strategies. This review will examine these nanoparticle-based strategies to immune modulation in detail, and discuss the promise and outstanding challenges facing the field of immune engineering from a chemical biology/materials engineering perspectiveNational Institutes of Health (U.S.) (Grants AI111860, CA174795, CA172164, AI091693, and AI095109)United States. Department of Defense (W911NF-13-D-0001 and Awards W911NF-07-D-0004

Readaptación a través del ejercicio en lesiones de ligamento cruzado anterior de rodilla

El trabajo realizado demuestra un proceso de Readaptación completo, explorando y actuando en el inicio y retorno de un caso en específico de lesión (ruptura) del ligamento cruzado anterior de rodilla en un sujeto. Se pondrá en juego el rol del Profesor o Licenciado en educación física, y el trabajo interdisciplinario con otros profesionales de la salud. Se presentará una evolución detallada con una planificación flexible, en base a objetivos a corto, mediano y largo plazo, orientada a las posibilidades y condiciones en las que el sujeto se encuentra, fomentando nuestro rol como educadores del cuerpo. Se argumentará el porqué de los ejercicios realizados (funciones y especificidades) y las evaluaciones pertinentes antes, durante y al finalizar dicho proceso. Presentaré, a través de fotografías distintos tipos de ejercicios detallados y se seleccionaré, diseñaré, y programaré estrategias que acompañarán al sujeto en el proceso de readaptación. Para finalizar, y a modo de conclusión explicaré lo enriquecedor que es realizar un trabajo en el marco de la interdisciplina.Fil: De Titta, Federico. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina

Evaluating the use of nanoparticles as an antigen delivery system

The delivery of antigens on degradable nanoparticles, directly to dendritic cells residing in lymph nodes, offers great opportunities for vaccine design. This master thesis investigates the issues related to the development of vaccines based on ultrasmall (25nm)nanoparticles, capable of draining to lymph nodes via lymphatic flow and to spontaneously activate complement factor C3 as an adjuvant. The first part investigates a Mycobacterium tuberculosis preventive vaccine in collaboration with Northwestern (Jamie Carter and Garrett Green) and EPFL students (Marie Ballester and Bastien Schyrr) in Cape Town. Research plan for the preclinical testing of potential vaccine formulations to be used as a tuberculosis vaccine was investigated as well as adjuvancy, antigen dosage determination, efficacy, safety testing, vaccine manufacture, regulatory issues, and transition to clinical trials. In the second part, a peptide derived from the Apical Membrane Antigen 1 (AMA1) of the malaria causing parasite Plasmodium falciparum, conjugated to 28nm nanoparticles was used to immunize mice and proved to create an immune response in 4 out of 11 mice after 4 injections. Antibodies produced by the responding mice were able to recognize the native antigen on the parasite in Indirect Immunofluorescence and Western blotting Assays. The nanoparticles were retrieved in mice lymph nodes by Immunohistochemistry and were located near antigen presenting cell