View clinical trials related to Innate Immune Response.
Filter by:To evaluate the bacterial-viral interactions between LPS and Fluenz as a model for sepsis (bacterial) and Influenza (viral) infections which are common and associated with high mortality rates in the ICU. To understand these interactions is important for the development of preventive and therapeutic interventions.
Neonatal morbidity and mortality from infectious diseases is of global concern. Childhood disease-specific immunisation is irrefutably linked to the decline in deaths from these targeted infections over the last century. However, neonatal immunisation is limited, in part, by the impaired adaptive immune function in this age group. There is now an expanding body of evidence for heterologous ('non-specific') effects of various vaccines used in childhood. This refers to the immunomodulatory capabilities of vaccines to influence immune outcomes beyond the vaccine's specific targeted disease. The underlying immunological mechanisms responsible for these effects are incompletely understood, but evidence is mounting that the innate immune system is central to these observed effects. This study is a randomised controlled trial designed to determine the influence of two commonly administered neonatal immunisations, BCG and Hepatitis B vaccine, given at birth, on the neonatal immune responses to non-specific antigens. The investigators will recruit 200 newborns at the Mercy Hospital for Women in Melbourne, Australia over a 1-year period. These babies will be allocated randomly to one of 4 groups, receiving these 2 vaccines in different combinations, at 2 set time points. (at birth and 1 week post randomisation) A blood sample will be taken at 1-week post randomisation for in vitro immunological analyses. This study will improve current understanding of the influence of vaccines on neonatal immunity and will help develop strategies exploiting beneficial heterologous ('non-specific') effects to improve protection against infection in the very young.
Rationale: The live attenuated Bacillus Calmette-Guerin (BCG) vaccine protects against extrapulmonary infection with Mycobacterium tuberculosis and leprosy. It has been shown that vaccination with BCG also leads to nonspecific protective effects, e.g. reduced infant mortality as a result of less severe infections, stimulation of the immune system in patients with bladder cancer and higher cytokine production upon restimulation of macrophages with non-related infectious pathogens in vitro. However, because the live attenuated BCG vaccine cannot be used in immune compromised hosts, the investigators would like to determine whether similar protective non-specific effects can be induced by γ-irradiated BCG. Objective: To determine whether vaccination with γ-irradiated BCG results in a higher cytokine response by monocytes upon restimulation in vitro with infectious pathogens, compared to monocytes before the vaccination. Study design: Explorative intervention trial. Study population: Healthy volunteers, 18 - 55 years old. Intervention: Healthy volunteers will be vaccinated with γ-irradiated BCG vaccine. Main study parameters/endpoints: Blood will be drawn before and at two different time points after vaccination with BCG to perform restimulation of isolated cells in vitro and compare cytokine production. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There is no known direct benefit for the volunteers to participate in the trial. The risks are negligible. BCG vaccination can cause pain and scarring at the site of injection, just as fever and headache. Local hematoma formation can occur at the site of the blood drawing. This will be minimized by the blood collection by experienced persons.
Excessive inflammation is associated with tissue damage caused by over-activation of the innate immune system. This can range from mild disease to extreme conditions, such as multiple organ dysfunction syndrome (MODS) and acute respiratory distress (ARDS). In marked contrast to adaptive immunity which is very sensitive to immune modulators such as steroids, the innate immune system cannot be sufficiently targeted by currently available anti-inflammatory drugs. The investigators hypothesize that pre-treatment with C1-esterase inhibitor in a human endotoxemia model can modulate the innate immune response. In this study, human endotoxemia will be used as a model for inflammation. Subjects will, prior to endotoxin administration, receive C1 esterase inhibitor or placebo. Blood will be sampled to determine the levels of markers of the innate immune response.
This will be a randomized study with the primary objective of assessing the impact of withholding versus encouraging breastfeeding on the immunogenicity of Rotarix® in infants. Enrolled subjects will all be administered Rotarix®, at ages 6 to 7 weeks, and at10 -14 weeks. The subjects will be randomized into one of the two study arms. In one of the group caregivers will be advised to breastfeed immediately prior to and after each dose of the vaccine while in the other group caregivers will be advised to withhold breastfeeding for 30 minutes before and after each dose of the vaccine. The other childhood vaccines i.e. OPV and Pentavalent will be administered at least 30 minutes after administration of Rotarix®, The enrolled subjects will be followed up for 4 weeks after the 2nd dose of Rotarix®.
The innate immune response is the first line of defense against invading pathogens. Ideally, the inflammatory response is tightly regulated leading to both adequate protection to invading pathogens as well as limitation of an exuberant or unwanted immune response such as seen in sepsis or auto-immune diseases. It has become increasingly clear that the autonomic nervous system (ANS) and the innate immune response are intimately linked. Activation of the sympathetic division of ANS dampens inflammation via β2-adrenoceptors. On the other hand, in some cases, sympathetic drive can also stimulate the inflammatory response via α2-adrenoceptors. The parasympathetic branch of the ANS modulates the inflammatory response as well, since it was discovered that electrical stimulation of the efferent vagus nerve in rats greatly inhibits the innate immune response. Generally, the ANS is regarded as pure autonomic which can not be influenced by behavior. However, trough special concentration/mediation techniques mastered by certain individuals, it might be possible to modulate ANS activity. In addition, recent unpublished findings indicate that these concentration/meditation techniques can also influence the inflammatory response ex vivo. In this study the investigators wish to investigate the effect of concentration/meditation on the innate immune response in vivo. In addition the investigators wish to elucidate the mechanism via which this effect is mediated. The investigators aim to use the so called human endotoxemia model. This model permits elucidation of key players in the immune response to a gram negative stimulus in vivo, therefore serving as a useful tool to investigate potential novel therapeutic strategies in a standardized setting. Objectives: Primary objective: The primary objective of the study is to determine the effect of concentration/meditation on the innate immune response induced by a lipopolysaccharide (LPS) challenge. Secondary Objective(s): 1. To determine the effects of concentration/meditation on ANS activity. Electroencephalography (EEG), heart-rate variability (HRV), muscle sympathetic nerve activity and plasma concentrations of catecholamines will be measured for this purpose. 2. To determine if concentration/meditation can attenuate (subclinical) renal damage known to occur during human endotoxemia, markers of proximal and distal tubular damage will be measured at various time points.