Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory blood pressure: a double-blind, randomised, placebo-controlled phase IIa study.

BACKGROUND: Hypertension can be controlled adequately with existing drugs such as angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Nevertheless, treatment success is often restricted by patients not adhering to treatment. Immunisation against angiotensin II could solve this problem. We investigated the safety and efficacy of CYT006-AngQb-a vaccine based on a virus-like particle-that targets angiotensin II to reduce ambulatory blood pressure. METHODS: In this multicentre, double-blind, randomised, placebo-controlled phase IIa trial, 72 patients with mild-to-moderate hypertension were randomly assigned with a computer-generated randomisation list to receive subcutaneous injections of either 100 mug CYT006-AngQb (n=24), 300 mug CYT006-AngQb (24), or placebo (24), at weeks 0, 4, and 12. 24-h ambulatory blood pressure was measured before treatment and at week 14. The primary outcomes were safety and tolerability. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00500786. FINDINGS: Two patients in the 100 mug group, three in the 300 mug group, and none in the placebo group discontinued study treatment. All patients were included in safety analyses; efficacy analyses did not include the five dropouts, for whom no data were available at week 14. Five serious adverse events were reported (two in the 100 mug group, two in the 300 mug group, and one in the placebo group); none were deemed to be treatment related. Most side-effects were mild, transient reactions at the injection site. Mild, transient influenza-like symptoms were seen in three patients in the 100 mug group, seven in the 300 mug group, and none in the placebo group. In the 300 mug group, there was a reduction from baseline in mean ambulatory daytime blood pressure at week 14 by -9.0/-4.0 mm Hg compared with placebo (p=0.015 for systolic and 0.064 for diastolic). The 300 mug dose reduced the early morning blood-pressure surge compared with placebo (change at 0800 h -25/-13 mm Hg; p<0.0001 for systolic, p=0.0035 for diastolic). INTERPRETATION: Immunisation with CYT006-AngQb was associated with no serious adverse events; most observed adverse events were consistent with local or systemic responses similar to those seen with other vaccines. The 300 mug dose reduced blood pressure in patients with mild-to-moderate hypertension during the daytime, especially in the early morning. FUNDING: Cytos Biotechnology AG.

Health Impact Assessment and Waste Management with particular reference to Incineration: An introductory paper

This introductory brief has been written as a response to a request for information on HIA and waste management, with particular reference to incineration. EU legislation forms the basis for much of Irish waste management policy. Waste Management – Taking Stock and Moving Forward (2004) sets targets for increased prevention and minimisation, encourages reuse and gives preference to recovery and recycling, which is in line with the EU’s Sixth Environmental Action Plan (2002). In the area of waste incineration, the Waste Incineration Directive (2000/76/EC) has been transposed into Irish law and sets operating requirements for the incineration of waste.

IPH Submission to Department of the Environment, Heritage and Local Government Climate Change Response Bill 2010

The main purpose of the Clmate Change Bill is to provide for the adoption of a national policy for reducing greenhouse gas (GHG) emissions; to support this through the making of mitigation and adaptation action plans; and to make provision for emission reduction targets to support the objective of transition to a low carbon, climate resilient and environmentally sustainable economy.The remit of the Institute of Public Health in Ireland (IPH) is to promote cooperation for public health between Northern Ireland and the Republic of Ireland in the areas of research and information, capacity building and policy advice. Our approach is to support Departments of Health and their agencies in both jurisdictions, and maximise the benefits of all-island cooperation to achieve practical benefits for people in Northern Ireland and the Republic of Ireland.IPH has a keen interest in the effects of climate change on health. In September 2010 the IPH published a paper – Climate Change and Health: A platform for action - to inform policy-makers and the public about the health benefits in reducing greenhouse gas emissions. This paper followed a seminar with international speakers, opened by Minister Gormley, on the same topic in February 2010. 

Immunopathology of cardiomyopathy in the experimental Chagas disease

The mechanisms by which Trypanosoma cruzi causes cardiomyopathy and induces neuronal destruction are discussed in this paper. The results suggest that autoimmunity in the chronic phase is the main cause of the progressive cardiac destruction, and that autoreactivity is restricted to the CD4+ T cell compartment. During the acute phase, the neuronal and cardiac fiber destruction occurs when ruptured parasite nests release T. cruzi antigens that bind to the cell surface in the vicinity which become targets for the cellular and humoral immune response against T. cruzi. The various factors involved in the genesis of autoimmunity in chronic T. cruzi infection include molecular mimicry, presentation of self-antigens and imbalance of immune regulation.

IPH response to DHSSPS Consultation on a ten year breastfeeding strategy for Northern Ireland 2012-2022

The Department of Health, Social Services and Public Safety invited submissions on the development of a new ten-year Breastfeeding Strategy for Northern Ireland 2012-2022 between May and September 2012. The draft Breastfeeding Strategy 2012 – 2022 proposes further action in relation to breastfeeding and aims to protect, promote, support and normalise breastfeeding within the population of Northern Ireland. Key points from IPH response IPH welcomes the commitment by the Department of Health, Social Services and Public Safety to develop a comprehensive long-term strategy to support women in Northern Ireland to breastfeed. The timeframe provides scope for developing clear long-term targets and actions and the embedding of breastfeeding culture into allied services, policies and programmes throughout Northern Ireland. The draft strategy’s recognition of the potential of breastfeeding as a means for tackling health inequalities forms a central theme of the IPH submission IPH welcomes the success achieved to date in improving breastfeeding. However, it is clear that the overall breastfeeding rate in Northern Ireland still lags behind the rest of the UK. Inequalities in breastfeeding rates remain an ongoing concern. IPH emphasises the importance of integrating the actions of the breastfeeding strategy with the strategic direction of overall public health policy in particular the forthcoming Fit and Well policy framework and early years strategies. IPH welcomes the inclusion of stipulations regarding weaning practices as an important component of the vision and one which, if achieved, will maximize the benefits from improving breastfeeding rates and duration.

IPH response to Department, Trade and Investment (NI) draft strategic energy framework

The draft Framework set out the proposed priorities for Northern Ireland's energy future over the next ten years or so and illustrates the key energy goals in term of competitiveness, security of energy supply, sustainablilty and infrastructure investment. It also proposes new and ambitious renewable electricity and renewable heat targets by 2020, which reflect the need for effected action against climate change and the need to address other policy goals in terms of security and sustainability of supply and costs.

IPH gives evidence to NI Assembly Health Committee Inquiry into Obesity

IPH Chief Executive, Dr Jane Wilde gave evidence to the Northern Ireland Assembly Health Committee inquiry into obesity. Dr Wilde recommended the following: Supporting the Department of Health’s strategic approach based on an understanding of the nature and complexity of obesity. Urgent and short term action to coordinate current activities and ensure focus on the most vulnerable. Exploring new forms and incentives to promote cross departmental work. Setting intermediate outcomes and targets Building stronger links between research, policy and practice, for example asking the Health Committee to set up a round table of researchers and policy makers Working systematically and transparently to identify key areas for cooperation with UK, Ireland and Europe Drawing from IPH work and other research, Dr Wilde briefed the Health Committee on the extent and impact of obesity, reasons for rising levels of obesity and the need for a stronger strategic response. She highlighted the importance of cross government action, the responsibilities of those beyond the health sector and the need for stronger evidence-informed policy and practice.

IPH Submission to the Department of Health and Children Statement of Strategy 2008-2010

The Department of Health and Children Statement of Strategy will map out in broad terms the Department’s key areas of strategic action in the coming three years and act as the backdrop against which the Business Plans of each division of the Department will be prepared. The Institute’s recent submission on the Department’s Strategy Statement proposes that tackling inequalities in health form a key area of strategic action across all divisions within the Department in the coming three years. The Institute called for the Department to make additional commitments to tackle health inequalities at their root causes, in addition to developing services to meet the needs of poor and vulnerable members of society. The submission states that the full implementation of the National Health Information Strategy is now a matter of urgency and also strongly recommends that the Department makes the achievement of the recommendations of the recent A Strategy for Cancer Control in Ireland a priority in the coming years within its enhanced policy evaluation and analysis role. A stronger leadership role to advance the vision set out in the Primary Care Strategy is encouraged. The submission also recommends the development of a new set of high-level long-term targets relating to the reduction of inequalities to provide an overarching policy context against which related policies and the HSE operations could be structured.

Response to Northern Ireland Housing Executive Review of Housing and Health

The Institute of Public Health in Ireland welcomes the opportunity to comment on the Northern Ireland Housing Executive (NIHE), Review of Housing and Health – Towards a Shared Agenda policy.   The Institute aims to improve health in Ireland, North and South by working to combat health inequalities and influence public policies in favour of health. The Institute recognises the potential health impacts linked with housing and welcome the proactive approach NIHE is adopting. By identifying the wider determinants of health, the NIHE acknowledges that as a statutory organization they have a major role to play in contributing to improved health for Northern Ireland.   There are many causal pathways linking housing to health and due to the nature of social housing, a number of vulnerable groups, for example those on a low income or the Travelling Community are subject to NIHE policies.  Overall the policy outlines a number of key recommendations.  The Institute advise that the Implementation Plan which will incorporate the recommendations should outline targets which can be measurable, for example, under Objective 1 which identifies the reduction of fuel poverty.  We recommend that key targets are outlined to show what action the NIHE has set in accordance to measure a reduction in fuel poverty.

Lassa virus entry in antigen presenting cells and evaluation of a novel nanoparticle vaccine platform against arena viruses

Arenaviruses are a large and diverse family of viruses that merit significant attention as causative agents of severe hemorrhagic fevers in humans. Lassa virus (LASV) in Africa and the South American hemorrhagic fever viruses Junin (JUNV), Machupo (MACV), and Guanarito (GTOV) have emerged as important human pathogens and represent serious public health problems in their respective endemic areas. A hallmark of fatal arenaviruses hemorrhagic fevers is a marked immunosuppression of the infected patients. Antigen presenting cells (APCs) such as macrophages and in particular dendritic cells (DCs) are early and preferred targets of arenaviruses infection. Instead of being recognized and presented as foreign antigens by DCs, arenaviruses subvert the normal mechanisms of pathogen recognition, invade DCs and establish a productive infection. Viral replication perturbs the DCs' ability to present antigens and to activate T and B cells, contributing to the marked virus-induced immunosuppression observed in fatal disease. Considering their crucial role in the development of an anti-viral immune response, the mechanisms by which arenaviruses, and in particular LASV, invade DCs are of particular interest. The C-type lectin DC-specific Intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) was recently identified as a potential entry receptor for LASV. The first project of my thesis focused therefore on the investigation of the role of DC-SIGN in LASV entry into primary human DCs. My data revealed that DC-SIGN serves as an attachment factor for LASV on human DCs and can facilitate capture of free virus and subsequent cell entry. However, in contrast to other emerging viruses, of the phlebovirus family, I found that DC-SIGN does likely not function as an authentic entry receptor for LASV. Moreover, I was able to show that LASV enters DCs via an unusually slow pathway that depends on actin, but is independent of clathrin and dynamin. Considering the lack of effective treatments and the limited public health infrastructure in endemic regions, the development of protective vaccines against arenaviruses is an urgent need. To address this issue, the second project of my thesis aimed at the development of a novel recombinant arenavirus vaccine based on a nanoparticle (NPs) platform and its evaluation in a small animal model. During the first phase of the project I designed, produced, and characterized suitable vaccine antigens. In the second phase of the project, I generated antigen-conjugated NPs, developed vaccine formulations, and tested the NPs for their ability to elicit anti-viral T cell responses as well as anti-viral antibodies. I demonstrated that the NPs platform is able to activate both cellular and humoral branches of the adaptive anti-viral immunity, providing proof-of-principle. In sum, my first project will allow, in a long term perspective, a better understanding of the viral pathogenesis and contribute to the development of novel antiviral strategies. The second project will expectidly offer a new treatment option against arenaviruses.