(Press-News.org) Boston, MA – Developing new vaccines to protect against diseases that plague humans is fraught with numerous challenges—one being that microbes tend to vary how they look on the surface to avoid being identified and destroyed by the immune system. However, researchers from Brigham and Women's Hospital (BWH) have discovered a sugar polymer that is common on the cell surface of several pathogens. This common sugar molecule makes it a promising target for the development of a broad-spectrum vaccine that can protect against numerous deadly microbes expressing this sugar on their cell surface.
The study will appear online in Proceedings of the National Academy of Sciences the week of May 27, 2013.
The researchers report that the sugar, known as beta-1-6-linked poly-N-acetyl glucosamine, or PNAG, is made by more bacterial, fungal, and other microbial organisms than previously thought. According to the researchers, antibodies produced naturally by humans and animals do not offer complete protection against microbes that express PNAG on their cell surface because the natural antibodies kill these microbes poorly.
Given this, the researchers created vaccine-induced, non-human-derived antibodies that would respond to a synthetic form of PNAG; and these antibodies had the properties needed for killing microbes. The researchers also tested a human-derived antibody that was able to bind to both the natural and synthetic forms of PNAG and could also kill microbes producing PNAG.
When the researchers injected mice with these antibodies, they observed protection against local and systemic infections caused by several unrelated pathogens, such as Streptococcus pyogenes, the cause of strep throat; Streptococcus pneumoniae, the cause of deadly pneumonias in the young and the elderly; Listeria monocytogenes, a cause of potentially fatal food poisoning; Neisseria meningitidis serogroup B, a serious cause of meningitis; Candida albicans, a very difficult to treat fungal infection; and, most surprisingly, a very potent strain causing malaria in mice, a surrogate for the most serious form of human malaria known as cerebral malaria.
The researchers also found the PNAG polymer on the surface of microbes that cause gonorrhea, trichomoniasis, serious gastrointestinal infections and typhoid fever. Additionally, they detected PNAG material on bacteria in tissues of humans with infections such as otitis media (ear infections) and tuberculosis—an important finding since it is critical that PNAG be produced during infection in order for the antibodies to do their job of killing and eliminating infectious agents.
"While we have known for awhile that staphylococci and several other bacteria including E. coli and some other microbes that cause hospital infections make PNAG, the new work expands this to a 'top 10 to 20' list of many of the major causes of serious human infections," said Gerald Pier, PhD, Division of Infectious Diseases, BWH Department of Medicine, Professor of Medicine, Microbiology and Immunobiology, Harvard Medical School, senior study author. "The possibility to use one agent to target so many different organisms including gonorrhea, TB and malaria is very exciting and unprecedented so far in the field of infectious diseases. However, whether or not one vaccine will work for any of these organisms, let alone many of them, will only be known once the vaccines and antibodies are thoroughly tested in humans."
A PNAG-based passive immunotherapy consisting of a fully human monoclonal antibody has been successfully tested in a phase I clinical trial for safety and pharmacokinetics in human volunteers, with no significant adverse events reported. Future testing will be conducted to further evaluate safety, dosage and effectiveness. A PNAG-based vaccine that can be injected into humans is also currently being produced with an expectation to begin human clinical trials in 2014.
###
This research was supported by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (AI46706, AI057159, U54 AI057159, 5R01AI079085-04, RO1AI079293).
Some of the study authors are inventors of intellectual properties (human monoclonal antibody to PNAG and PNAG vaccines) which are licensed by Brigham and Women's Hospital to Alopexx Vaccine, LLC, and Alopexx Pharmaceuticals, LLC. Sanofi was involved in some of the pre-clinical studies conducted in the study and have license rights to the human monoclonal antibody for clinical trials.
Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in New England and employs more than 15,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving nearly 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $625 million in funding. BWH continually pushes the boundaries of medicine, including building on its legacy in organ transplantation by performing the first face transplants in the U.S. in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies, OurGenes and the Women's Health Initiative. For more information and resources, please visit BWH's online newsroom.
All in one shot
A sugar polymer found on the cell surface of multiple pathogens could be key to developing a broad-spectrum vaccine
2013-05-28
ELSE PRESS RELEASES FROM THIS DATE:
When doctors and patients share in decisions, hospital costs go up
2013-05-28
Since the 1980s, doctors and patients have been encouraged to share decision making. Proponents argue that this approach promotes doctor-patient communication, enhances patient satisfaction, improves health outcomes, and even may lower cost.
Yet, a hospital-based study found that patients who want to participate in their medical decisions end up spending more time in the hospital and raising costs of their hospital stay by an average of $865.
The findings, published in JAMA Internal Medicine, came from the first hospital-based study to examine how patients' desire ...
Meta-analysis: Bug and weed killers, solvents may increase risk of Parkinson's disease
2013-05-28
MINNEAPOLIS – A large analysis of more than 100 studies from around the world shows that exposure to pesticides, or bug and weed killers, and solvents is likely associated with a higher risk of developing Parkinson's disease. The research appears in the May 28, 2013, print issue of Neurology®, the medical journal of the American Academy of Neurology.
"Due to this association, there was also a link between farming or country living and developing Parkinson's in some of the studies," said study author Emanuele Cereda, MD, PhD, with the IRCCS University Hospital San Matteo ...
Should you stop blood thinners before surgery? AAN guideline provides direction
2013-05-28
MINNEAPOLIS – A new guideline from the American Academy of Neurology will help people who take blood thinners decide whether or not to take them during surgery or other medical procedures. The guideline is published in the May 28, 2013, print issue of Neurology®, the medical journal of the American Academy of Neurology.
People who have had a stroke often take blood thinners such as aspirin or warfarin to prevent another stroke. Blood thinners, or anticlotting drugs, are also used to prevent a first stroke in people with atrial fibrillation, an irregular or fast heartbeat. ...
Stem cell injections improve spinal injuries in rats
2013-05-28
An international team led by researchers at the University of California, San Diego School of Medicine reports that a single injection of human neural stem cells produced neuronal regeneration and improvement of function and mobility in rats impaired by an acute spinal cord injury (SCI).
The findings are published in the May 28, 2013 online issue of Stem Cell Research & Therapy.
Martin Marsala, MD, professor in the Department of Anesthesiology, with colleagues at UC San Diego and in Slovakia, the Czech Republic and The Netherlands, said grafting neural stem cells derived ...
Down syndrome neurons grown from stem cells show signature problems
2013-05-28
Madison, Wis. – Down syndrome, the most common genetic form of intellectual disability, results from an extra copy of one chromosome. Although people with Down syndrome experience intellectual difficulties and other problems, scientists have had trouble identifying why that extra chromosome causes such widespread effects.
In new research published this week, Anita Bhattacharyya, a neuroscientist at the Waisman Center at the University of Wisconsin-Madison, reports on brain cells that were grown from skin cells of individuals with Down syndrome.
"Even though Down ...
Communication between physicians and patients important for expectations
2013-05-28
Seriously ill patients undergoing hemodialysis are more optimistic about their prognosis and prospects for transplants than their nephrologists, according to a study published online by JAMA Internal Medicine. The study also found that nephrologists rarely had discussed estimates of life-expectancy with their patients.
Melissa W. Wachterman, M.D., M.P.H., from Veterans Affairs Boston Health Care System and colleagues compared patients' and physicians' expectations about one- and five-year survival rates and transplant candidacy among 207 patients undergoing hemodialysis ...
Patient participation in decision making associated with increased costs, services
2013-05-28
A survey of almost 22,000 admitted patients at the University of Chicago Medical Center found patient preference to participate in decision making concerning their care was associated with a longer length of stay and higher total hospitalization costs, according to a report published online by JAMA Internal Medicine.
Hyo Jung Tak, Ph.D., and colleagues examined the relationship between patient preferences for participation in medical decision making and health care utilization among patients hospitalized between July 1, 2003 and August 31, 2011 by asking patients to ...
How patient centered are medical decisions?
2013-05-28
A national survey sample of adults who had discussions with their physicians in the preceding two years about common medical tests, medications and procedures often did not reflect a high level of shared decision making, according to an article published online by JAMA Internal Medicine.
Floyd J. Fowler, Jr., Ph.D., from the Informed Medical Decisions Foundation and the University of Massachusetts, Boston, conducted a 2011 survey of a cross section of U.S. adults 40 years or older and asked them to indicate whether they reported making one of 10 medical decisions and ...
Decision making preferences among patients with heart attacks
2013-05-28
In a research letter, Harlan M. Krumholz, M.D., S.M., from Yale University School of Medicine and colleagues, "sought to investigate preferences for participation in the decision-making process among individuals hospitalized with an acute myocardial infarction ([AMI] or heart attack)." The researchers combined data from two similar AMI registries (TRIUMPH and PREMIER) which resulted in 6,636 patients in the study sample who were asked about who should make decisions on treatment options.
"More than two-thirds of patients with AMI indicated a preference to play an active ...
Increase in unintentional marijuana ingestion among children following new drug laws in Colorado
2013-05-28
Following modification of drug enforcement laws for possession of marijuana in Colorado, there was an apparent increase in unintentional marijuana ingestions by young children, according to a report and accompanying editorials published Online First by JAMA Pediatrics, a JAMA Network publication.
Several states and Washington, D.C. have enacted laws to decriminalize medical marijuana and two states, Colorado and Washington, have passed amendments to legalize the recreational use of marijuana. In late 2009, the Justice Department issued a policy instructing federal prosecutors ...
LAST 30 PRESS RELEASES:
New strategies to enhance chiral optical signals unveiled
Cambridge research uncovers powerful virtual reality treatment for speech anxiety
2025 Gut Microbiota for Health World Summit to spotlight groundbreaking research
International survey finds that support for climate interventions is tied to being hopeful and worried about climate change
Cambridge scientist launches free VR platform that eliminates the fear of public speaking
Open-Source AI matches top proprietary model in solving tough medical cases
Good fences make good neighbors (with carnivores)
NRG Oncology trial supports radiotherapy alone following radical hysterectomy should remain the standard of care for early-stage, intermediate-risk cervical cancer
Introducing our new cohort of AGA Future Leaders
Sharks are dying at alarming rates, mostly due to fishing. Retention bans may help
Engineering excellence: Engineers with ONR ties elected to renowned scientific academy
New CRISPR-based diagnostic test detects pathogens in blood without amplification
Immunotherapy may boost KRAS-targeted therapy in pancreatic cancer
Growing solar: Optimizing agrivoltaic systems for crops and clean energy
Scientists discover how to reactivate cancer’s molecular “kill switch”
YouTube influencers: gaming’s best friend or worst enemy?
uOttawa scientists use light to unlock secret of atoms
NJIT mathematician to help map Earth's last frontier with Navy grant
NASA atmospheric wave-studying mission releases data from first 3,000 orbits
‘Microlightning’ in water droplets may have sparked life on Earth
Smoke from wildland-urban interface fires more deadly than remote wildfires
What’s your body really worth? New AI model reveals your true biological age from 5 drops of blood
Protein accidentally lassos itself, helping explain unusual refolding behavior
With bird flu in raw milk, many in U.S. still do not know risks of consuming it
University of Minnesota research team awarded $3.8 million grant to develop cell therapy to combat Alzheimer’s disease
UConn uncovers new clue on what is leading to neurodegenerative diseases like Alzheimer’s and ALS
Resuscitation in out-of-hospital cardiac arrest – it’s how quickly it is done, rather than who does it
A closer look at biomolecular ‘silly putty’
Oxytocin system of breastfeeding affected in mothers with postnatal depression
Liquid metal-enabled synergetic cooling and charging: a leap forward for electric vehicles
[Press-News.org] All in one shotA sugar polymer found on the cell surface of multiple pathogens could be key to developing a broad-spectrum vaccine