(Press-News.org) Researchers have identified a section of the anthrax toxin Lethal Factor that could help produce a more effective vaccine.
Anthrax is a potentially lethal disease caused by a bacterium called Bacillus anthracis. The bacteria produce spores that when inhaled, ingested or absorbed into the skin release toxins. When anthrax affects the lungs or intestines it can cause death within a few days whilst infection of the skin (cutaneous anthrax) is less dangerous.
Infection can occur from contact with infected livestock, meat or hides, but most people know about anthrax from its use as a biological weapon, notably in the 2001 attacks through the US postal system. The anthrax bacterium can be used in this way because its spores survive for long amounts of time and are easily reproduced.
The international research team led by Professor Danny Altmann from Imperial College London was funded by US National Institute of Health (NIH) to explore a new form of vaccine against the anthrax bacterium. Published in PLOS Pathogens the study focussed on the part of the toxin known as the 'Lethal Factor' (LF). The interest in LF was triggered by research on a cohort of Turkish farmers who had developed natural immunity to the less dangerous form of cutaneous anthrax.
By studying this group and using a mouse model, the researchers mapped the regions of the LF toxin targeted by protective T lymphocytes (a type of white cell that is essential for human immunity). They found a specific part that could form the basis for a vaccine since it elicits a highly effective immune response and works across a wide range of people. Using this section of the LF protein they successfully protected mice against the toxic effects of the anthrax bacterium.
Professor Altmann from Imperial College London's Department of Medicine said: "We have discovered a tiny section of protein that could potentially protect against this horrific disease. Although we mostly work at the molecular level of immunity we wanted to start with the bigger picture so we studied a community of Turkish farmers exposed to anthrax to see how their natural immunity had developed."
Vaccination works by stimulating our immune systems to make protective antibodies. The toxic effects of anthrax are caused by a combination of three proteins – Protective Antigen (PA), Edema factor (EF) and Lethal Factor (LF). On their own each of these individual proteins are not toxic but they can still produce an immune response in terms of stimulating white blood cells. This makes them potential candidates on which to base a vaccine.
Initial anthrax vaccines used weakened forms of the anthrax spore, which produced some concerning side effects. More recently researchers have developed next generation vaccines to protect the military against bioterrorism.
Until now these have focussed on the Protective Antigen (PA) protein as a means to stimulate the immune system but these vaccines require extensive treatment regimes and there are concerns about effectiveness and longevity. Research on immunity in the Turkish farmers who had developed cutaneous anthrax indicated they had developed a natural immune response to both PA and LF, suggesting that immunity to the Lethal Factor (LF) protein may contribute to protection.
Working both with blood samples from the previously infected farmers and with a mouse model, the researchers confirmed that LF protein provoked a strong immune response to anthrax. They honed in on two particular sections, or peptides, that make up the protein (LF 457-476 and LF 467-486), which stimulated particularly strong immunity and produced this effect over a wide range of genetic differences in 'tissue type'. This increases the chance that a vaccine based on these peptides would offer protection across genetically diverse human populations.
Finally, in collaboration with a team at the Defence Science and Technology Laboratory Porton Down, the researchers treated mice with a vaccine based on this region of the LF protein. This was shown to provide protection to the mice against the toxic effects of anthrax bacterium.
"Perhaps 90 per cent of research into anthrax vaccines has looked at PA but there are many other proteins to consider, including LF," said Professor Altmann. "In this research we are not trying to revolutionise current vaccines, which is a long-haul process. Rather we are trying to demystify the immunology of this frightening infection, hopefully providing clues to help develop future vaccines."
INFORMATION:
The research was a collaboration with researchers from Imperial College London, University of Newcastle, Defence Science and Technology Laboratory Porton Down, University of Maryland USA and the Commissariat à l'énergie Atomique France.
The study was funded through the US NIH Epitope Discovery Programme
For more information please contact:
Franca Davenport
Research Media Officer
Imperial College London
Email: f.davenport@imperial.ac.uk
Tel: +44(0)20 7594 2198
Out of hours duty press officer: +44(0)7803 886 248
Notes to editors
Reference: S.Ascough et al. 'Anthrax lethal factor as an immune target in humans and transgenic mice and the impact of HLA polymorphism on CD4+ T cell immunity' PLOS Pathogens (2014) http://dx.plos.org/10.1371/journal.ppat.1004085.
About Imperial College London
Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.
Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of energy and address security challenges.
In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.
Website: http://www.imperial.ac.uk
10-year study shows 'Lethal Factor' could be X-factor for new anthrax vaccine
2014-05-02
ELSE PRESS RELEASES FROM THIS DATE:
Breaking up water: Controlling molecular vibrations to produce hydrogen
2014-05-02
Natural gas (methane) can be converted into hydrogen (H2), which is used in clean energy, synthetic fertilizers, and many other chemicals. The reaction requires water and a nickel catalyst. Methane and water molecules attach on the catalyst's surface, where they dissociate into their atomic components. These then recombine to form different compounds like H2 and CO. Previous research has focused mainly on understanding how methane dissociates, but experimental constraints have limited research into water dissociation. Publishing in Science, EPFL scientists have used lasers ...
Climate change study reveals unappreciated impacts on biodiversity
2014-05-02
Shrinking ice sheets and melting ice caps are well known consequences of climate change. But a new study reveals that impacts on biodiversity will be just as severe in other regions of the world. When multiple dimensions of climate change are analyzed, different regions emerge as threatened by different aspects of climate change. The tropics, for example, will be highly affected by local changes in temperature and precipitation, leading to novel climates with no current analogues in the planet. These results, recently published in Science, expose the complexities of climate ...
The Lancet and The Lancet Respiratory Medicine: Controlling, diagnosing, and preventing asthma
2014-05-02
On Friday 2 May, 2014, The Lancet and The Lancet Respiratory Medicine will release three new review articles and an Editorial on asthma, ahead of World Asthma Day on May 6 and the American Thoracic Society's international conference (ATS 2014) in San Diego (May 16-21).
Editorial – Controlling asthma
Outdoor air pollution and asthma
Asthma genetics and personalised medicine
Diagnosis, management, and prognosis of preschool wheeze
The Lancet: Outdoor air pollution and asthma
Traffic and power generation are the main sources of urban air pollution. The idea that ...
Connection between genetic variation and immune system, risk for neurodegenerative and other disease
2014-05-02
Boston and Cambridge, MA – Researchers from Brigham and Women's Hospital (BWH), Harvard Medical School (HMS), the Broad Institute of MIT and Harvard, Massachusetts General Hospital (MGH), and University of Chicago report findings demonstrating how genetic variations among healthy, young individuals can influence immune cell function. Many of those variants are also genetic risk factors for common diseases such as Alzheimer's disease, diabetes, and multiple sclerosis later in life, offering new insight into disease pathology.
The study will be published in the May 2, ...
Delving deep into the brain
2014-05-02
CAMBRIDGE, MA -- Launched in 2013, the national BRAIN Initiative aims to revolutionize our understanding of cognition by mapping the activity of every neuron in the human brain, revealing how brain circuits interact to create memories, learn new skills, and interpret the world around us.
Before that can happen, neuroscientists need new tools that will let them probe the brain more deeply and in greater detail, says Alan Jasanoff, an MIT associate professor of biological engineering. "There's a general recognition that in order to understand the brain's processes in comprehensive ...
US corn yields are increasingly vulnerable to hot, dry weather, Stanford research shows
2014-05-02
Corn yields in the central United States have become more sensitive to drought conditions in the past two decades, according to Stanford research.
The study, which appears in the journal Science, was led by Stanford's David Lobell, associate professor of environmental Earth system science and associate director of the Center on Food Security and the Environment. "The Corn Belt is phenomenally productive," Lobell said, referring to the region of Midwestern states where much of the country's corn is grown. "But in the past two decades we saw very small yield gains in non-irrigated ...
New insights into bacterial substitute for sex
2014-05-02
Bacteria don't have sex as such, but they can mix their genetic material by pulling in DNA from dead bacterial cells and inserting these into their own genome.
New research led by Imperial College London has found that this process – called recombination – is more complex than was first thought. The findings, published today in PLoS Genetics, could help us understand why bacteria which cause serious diseases are able to evade vaccines and rapidly become drug-resistant.
Dr Rafal Mostowy of Imperial College London's School of Public Health explains: "During recombination, ...
Clinical opinion published in American Journal of Obstetrics and Gynecology
2014-05-02
When a woman requires gynecologic surgery, she and her surgeon have several minimally invasive surgical options, including robotic surgery. In recent years, the use of robotic surgery has become more and more common. But questions have arisen about the potential overuse of robotic surgery and its advantages over traditional laparotomy for hysterectomy.
A clinical opinion by Charles Rardin, MD, a urogynecologist in the Division of Urogynecology and Reconstructive Surgery and director of the Robotic Surgery Program for Women at Women & Infants Hospital of Rhode Island, ...
Elevated liver enzyme levels linked to higher gestational diabetes risk
2014-05-02
OAKLAND, Calif., May 2, 2014 — Women with high levels of a common liver enzyme measured prior to pregnancy were twice as likely to subsequently develop gestational diabetes than those with the lowest levels, according to a Kaiser Permanente study published today in the journal Diabetes Care.
The liver plays an important role in regulating glucose levels in the body. The liver enzyme, called gamma-glutamyl transferase (known as GGT), is a common marker of liver function and has also been associated with insulin resistance, which can be a precursor to gestational diabetes ...
MERS coronavirus can be transmitted from camel to man
2014-05-02
The so-called Middle East respiratory syndrome (MERS) coronavirus was first found in June 2012 in a patient from Saudi Arabia, who suffered from severe pneumonia. Since this time more than 300 persons have developed an infection, of whom about a third died. The fact that the Arabian camel is the origin of the infectious disease has been confirmed recently. The transmission pathways of the viruses, however, have not been clear until now.
Viruses in humans and camels from one region are identical
Virologists Norbert Nowotny and Jolanta Kolodziejek from the Institute ...