BreakThrough Digest Medical News |
- Compound discovered that boosts effect of vaccines against HIV and flu
- New device to remove stroke-causing blood clots proves better than standard tool
- Diagnostic test shows potential to noninvasively identify significant coronary artery disease
| Compound discovered that boosts effect of vaccines against HIV and flu Posted: 25 Aug 2012 09:00 PM PDT
Oxford University scientists have discovered a compound that greatly boosts the effect of vaccines against viruses like flu, HIV and herpes in mice. An ‘adjuvant’ is a substance added to a vaccine to enhance the immune response and offer better protection against infection.
The Oxford University team, along with Swedish and US colleagues, have shown that a type of polymer called polyethyleneimine (PEI) is a potent adjuvant for test vaccines against HIV, flu and herpes when given in mice. The researchers were part-funded by the UK Medical Research Council and report their findings in the journal Nature Biotechnology. Mice given a single dose of a flu vaccine including PEI via a nasal droplet were completely protected against a lethal dose of flu. This was a marked improvement over mice given the flu vaccine without an adjuvant or in formulations with other adjuvants. The Oxford researchers now intend to test the PEI adjuvant in ferrets, a better animal model for studying flu. They also want to understand how long the protection lasts for. It is likely to be a couple of years before a flu vaccine using the adjuvant could be tested in clinical trials in humans, the researchers say. ‘Gaining complete protection against flu from just one immunisation is pretty unheard of, even in a study in mice,’ says Professor Quentin Sattentau of the Dunn School of Pathology at Oxford University, who led the work. ‘This gives us confidence that PEI has the potential to be a potent adjuvant for vaccines against viruses like flu or HIV, though there are many steps ahead if it is ever to be used in humans.’ HIV, flu and herpes are some of the most difficult targets to develop vaccines against. HIV and flu viruses are able to change and evolve to escape immune responses stimulated by vaccines. There aren’t any effective vaccines against HIV and herpes as yet, and the flu vaccine needs reformulating each year and doesn’t offer complete protection to everyone who receives it. Finding better adjuvants could help in developing more effective vaccines against these diseases. Most vaccines include an adjuvant. The main ingredient of the vaccine ? whether it is a dead or disabled pathogen, or just a part of the virus or bacteria causing the disease ? primes the body’s immune system so it knows what to attack in case of infection. But the adjuvant is needed as well to stimulate this process. While the need for adjuvants in vaccines has been recognised for nearly 100 years, the way adjuvants work has only recently been understood. The result has been that only a small set of adjuvants is used in current vaccines, often for historical reasons. The most common adjuvant by far is alum, an aluminium-containing compound that has been given in many different vaccines worldwide for decades. However, alum is not the most potent adjuvant for many vaccine designs. ‘There is a need to develop new adjuvants to get the most appropriate immune response from vaccines,’ says Professor Sattentau, who is also a James Martin Senior Fellow at the Oxford Martin School, University of Oxford. The Oxford University team found that PEI, a standard polymer often used in genetic and cell biology, has strong adjuvant activity. When included in a vaccine with a protein from HIV, flu or herpes virus, mice subsequently mounted a strong immune response against that virus. The immune response was stronger than with other adjuvants that are currently being investigated. The team also showed that PEI is a potent adjuvant in rabbits, showing the effect is not just specific to mice and could be general. Another potential advantage of PEI is that it works well as an adjuvant for ‘mucosal vaccines’. These vaccines are taken up the nose or in the mouth and absorbed through the mucus-lined tissues there, getting rid of any pain and anxiety from a needle. Mucosal vaccines may also be better in some ways as mucosal tissues are the sites of infection for these diseases (airways for respiratory diseases, genital mucosa for HIV and herpes). Professor Sattentau suggests that: ‘In the best of all possible worlds, you could imagine people would have one dose of flu vaccine that they’d just sniff up their nose or put under their tongue. And that would be it: no injections and they’d be protected from flu for a number of years. ‘It’s just a vision for the future at the moment, but this promising adjuvant suggests it is a vision that is at least possible.’ ### Notes to Editors
* The body’s immune system is made up of two arms: the innate immune system and the adaptive immune system. The adaptive immune system consists of the antibodies and immune cells (T and B cells) the body develops specifically to combat a particular foreign agent. The innate immune system had been thought of as playing a more primitive, non-specific role in protecting against invaders like viruses and parasites. However, it is now realised that the innate immune system is essential in kicking off any immune response. It needs to be activated first to generate an adaptive immune response. But the innate immune system doesn’t just press the start button. It tailors the body’s adaptive immune response, deciding on what particular mix of antibodies and T cells is needed and teaching them what to attack. It is the adjuvants in vaccines that stimulate the innate immune system. So having the right adjuvant can help the body produce the most appropriate immune response to protect against future infection. * The paper ‘Polyethyleneimine is a potent mucosal adjuvant for glycoproteins with innate and adaptive immune activating properties’ is to be published in the journal Nature Biotechnology with an embargo of 18:00 UK time / 13:00 US Eastern time on Sunday 26 August 2012. * The study was funded by the UK Medical Research Council, European Commission, the International AIDS Vaccine Initiative (IAVI), the Bill and Melinda Gates Foundation and Dormeur Investment Service Ltd. * Professor Sattentau is an investigator in the Jenner Institute at Oxford University and a James Martin Senior Fellow at the Oxford Martin School, Oxford University. * For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including one of the first antibiotics penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. www.mrc.ac.uk * The Oxford Martin School
is a unique interdisciplinary community within the University of Oxford. The School fosters innovative thinking, deep scholarship and collaborative activity to address the most pressing risks and realise new opportunities of the 21st century. It was founded in 2005 through the vision and generosity of James Martin, and currently comprises over 35 interdisciplinary research programmes on global future challenges. The Oxford Martin School’s Director is Ian Goldin, Professor at the University of Oxford. http://www.oxfordmartin.ox.ac.uk * Oxford University’s Medical Sciences Division is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students. The University is rated the best in the world for medicine, and it is home to the UK’s top-ranked medical school. From the genetic and molecular basis of disease to the latest advances in neuroscience, Oxford is at the forefront of medical research. It has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic. Partnerships with the local NHS Trusts enable patients to benefit from close links between medical research and healthcare delivery. A great strength of Oxford medicine is its long-standing network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies which examine the role of factors such as smoking, alcohol and diet on cancer, heart disease and other conditions. Contact: University of Oxford |
| New device to remove stroke-causing blood clots proves better than standard tool Posted: 25 Aug 2012 09:00 PM PDT Stroke is the fourth leading cause of death and a common cause of long-term disability in the United States, but doctors have very few proven treatment methods. Now a new device that mechanically removes stroke-causing clots from the brain is being hailed as a game-changer.
In a recent clinical trial, the SOLITAIRE Flow Restoration Device dramatically outperformed the standard mechanical treatment. Findings from the trial, called SOLITAIRE With the Intention for Thrombectomy (SWIFT), are published online today in the journal The Lancet and will also appear in a later print edition of the journal. SOLITAIRE, which was approved by the U.S. Food and Drug Administration in March, is among an entirely new generation of devices designed to remove blood clots from blocked brain arteries in patients experiencing an ischemic stroke. It has a self-expanding, stent-like design, and once inserted into a blocked artery using a thin catheter tube, it compresses and traps the clot. The clot is then removed by withdrawing the device, reopening the blocked blood vessel. “This new device is significantly changing the way we can treat ischemic stroke,” said the study’s lead author, Dr. Jeffrey L. Saver, director of the UCLA Stroke Center and a professor of neurology at the David Geffen School of Medicine at UCLA. “We are going from our first generation of clot-removing procedures, which were only moderately good in reopening target arteries, to now having a highly effective tool.” Results of the study showed that the device opened blocked vessels without causing symptomatic bleeding in or around the brain in 61 percent of patients. The standard FDA?approved mechanical device ? a corkscrew-type clot remover called the MERCI Retriever ? was effective in 24 percent of cases. The use of SOLITAIRE also led to better survival three months after a stroke. There was a 17.2 percent mortality rate with the new device, compared with a 38.2 percent rate with the older one. About 87 percent of all strokes are caused by blood clots blocking a blood vessel supplying the brain. The stroke treatment that has received the most study is an FDA?approved clot-busting drug known as tissue plasminogen activator, but this drug must be given within four-and-a-half hours of the onset of stroke symptoms, and even more quickly in older patients. When clot-busting drugs cannot be used or are ineffective, the clot can sometimes be mechanically removed during, or beyond, the four-and-a-half?hour window. The current study, however, did not compare mechanical clot removal to drug treatment. For the trial, researchers randomly assigned 113 stroke patients at 18 hospitals to receive either SOLITAIRE or MERCI therapy within eight hours of stroke onset, between January 2010 and February 2011. The patients’ average age was 67, and 68 percent were male. The time from the beginning of stroke symptoms to the start of the clot-retriever treatment averaged 5.1 hours. Forty percent of the patients had not improved with standard clot-busting medication prior to the study, while the remainder had not received it. At the suggestion of a safety monitoring committee, the trial was ended nearly a year earlier than planned due to significantly better outcomes with the experimental device. Other statistically significant findings included:
“Nearly a decade ago, our UCLA Stroke Center team invented the first stroke retrieval device ? the MERCI Retriever ? and now we are pleased to have helped develop and successfully test a superior, next-generation clot removing device,” said Dr. Reza Jahan, associate professor of radiology at UCLA and the study’s principal neurointerventional investigator, who also led the pre-clinical studies. “It is exciting to have a highly effective new tool that can improve the outcomes for more stroke patients.” ### Additional co-authors included Dr. Elad Levy, Dr. Tudor G. Jovin, Dr. Blaise Baxter, Dr. Raul Nogueira, Dr. Wayne Clark, Dr. Ronald Budzik, Dr. Osama O. Zaidat and the SWIFT trial investigators. Covidien, the manufacturer of the SOLITAIRE device, funded the study. The SOLITAIRE device is cleared by the FDA for use in the United States and is also approved for use in Europe. Saver and Jahan received compensation from Covidien as scientific consultants for the design and conduct of the trial. The UCLA Stroke Center, recognized as one of the world’s leading centers for the management of cerebral vascular disease, treats simple and complex vascular disorders by incorporating recent developments in emergency medicine, stroke neurology, microneurosurgery, interventional neuroradiology, stereotactic radiology, neurointensive care, neuroanesthesiology and rehabilitation neurology. The program is unique in its ability to integrate clinical and research activities across multiple disciplines and departments. Founded in 1994, the UCLA Stroke Center is designated as a certified Primary Stroke Center by the national Joint Commission on Accreditation of Healthcare Organizations. For more news, visit the UCLA Newsroom and follow us on Twitter. Contact: Amy Albin |
| Diagnostic test shows potential to noninvasively identify significant coronary artery disease Posted: 25 Aug 2012 09:00 PM PDT
Among patients with suspected or known coronary artery disease, use of a method that applies computational fluid dynamics to derive certain data from computed tomographic (CT) angiography demonstrated improved diagnostic accuracy vs. CT angiography alone for the diagnosis of ischemia, according to a study being published online by JAMA. The study is being released early to coincide with its presentation at the European Society of Cardiology Congress.
“Coronary computed tomographic angiography is a noninvasive anatomic test for diagnosis of coronary stenosis [narrowing of a blood vessel] that does not determine whether a stenosis causes ischemia [inadequate blood supply]. In contrast, fractional flow reserve (FFR) is a physiologic measure of coronary stenosis expressing the amount of coronary flow still attainable despite the presence of a stenosis, but it requires an invasive procedure. Noninvasive FFR computed from CT (FFRCT) is a novel method for determining the physiologic significance of coronary artery disease (CAD), but its ability to identify ischemia has not been adequately examined to date,” according to background information in the article. James K. Min, M.D., of the Cedars-Sinai Heart Institute, Los Angeles, and colleagues conducted a study to evaluate the performance of noninvasive FFRCT compared with an invasive FFR reference standard for diagnosis of ischemia. The study included 252 patients with suspected or known CAD from 17 centers in 5 countries who underwent CT, invasive coronary angiography (ICA), FFR, and FFRCT between October 2010 and October 2011. About 77 percent of patients had experienced angina within the last month. Ischemia was defined by certain criteria. Anatomically obstructive CAD was defined by a stenosis of 50 percent or larger on CT and ICA. Among 615 study vessels, 271 had less than 30 percent stenosis and 101 had at least 90 percent stenosis. Among study participants, 137 (54.4 percent) had an abnormal FFR as determined by ICA. The researchers found that the diagnostic accuracy for FFRCT plus CT was 73 percent, which did not meet a prespecified primary end point for accuracy (as pre-specified based on the lower limit of a calculated 95 percent confidence interval). By comparison, diagnostic accuracy of CT alone for detecting coronary lesions with stenosis of 50 percent or greater, was 64 percent. When comparing FFRCT alone with CT alone for detecting these lesions, FFRCT demonstrated superior discrimination. “On a per-patient basis, diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of FFRCT plus CT were 73 percent, 90 percent, 54 percent, 67 percent, and 84 percent, respectively,” the authors write. They note that the sensitivity and negative predictive value of FFRCT were high, indicating a low rate of false-negative studies. “These diagnostic features of FFRCT may encourage a greater sense of diagnostic certainty that patients who undergo CT who have ischemia are not overlooked, such that clinicians may be confident in not proceeding to invasive angiography in patients with stenoses on CT when FFRCT results are normal.” “Taken together, these study results suggest the potential of FFRCT as a promising noninvasive method for identification of individuals with ischemia.” (doi:10.1001/2012.jama.11274. Available pre-embargo to the media at http://media.jamanetwork.com) Editor’s Note: This study was funded by HeartFlow Inc. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc. Editorial: Detecting Obstructive Coronary Disease With CT Angiography and Noninvasive Fractional Flow Reserve
In an accompanying editorial, Manesh R. Patel, M.D., of Duke University Medical Center, Durham, N.C., writes that future studies with the FFRCT technology “should be aimed at diagnostic strategies involving patients with varying pretest risks, thereby providing information on the incremental benefit from the test.” “Additionally, important comparison technologies beyond invasive angiography are needed, although improved access techniques and safety of invasive FFR may make it a plausible comparator. In addition to diagnostic performance, other outcomes of interest such as resource utilization and clinical outcomes should be captured. Finally, future studies will need to have local sites rather than core laboratories perform, analyze, and interpret the images to provide a sense of real-world function. It is with these types of continued rigorous studies that noninvasive technologies such as FFRCT plus CT may move the clinical community closer to the holy grail of a high-quality combined anatomic and functional test for detection of CAD that improves efficiency and patient outcomes.” (doi:10.1001/2012.jama.11383. Available pre-embargo to the media at http://media.jamanetwork.comContact: Sally Stewart
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