Tuesday, April 9, 2019
A research team led by scientists from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) has determined how several antibodies induced by Epstein-Barr virus (EBV), a herpesvirus that causes infectious mononucleosis and is associated with certain cancers, block infection of cells grown in the laboratory. They then used this information to develop novel vaccine candidates that, in animals, elicited potent anti-EBV antibody responses that blocked infection of cell types involved in EBV-associated cancers.
Currently, there is no licensed vaccine for EBV. The virus is associated with certain cancers (nasopharyngeal and gastric) of epithelial cells, which form the lining of the body’s surfaces, as well as Burkitt and Hodgkin lymphomas, which are cancers of the immune system’s B cells. Worldwide, about 200,000 cases of EBV-associated cancers occur annually, resulting in 140,000 deaths.
Jeffrey I. Cohen, M.D., and Wei Bu, Ph.D., both of NIAID, led the investigation. Prior efforts to develop an EBV vaccine focused on a viral surface protein, gp350, that the virus uses to enter B cells. However, EBV infects not only B cells, but also epithelial cells that line the mouth and upper throat. These cells are usually infected after contact with saliva from an EBV-infected individual. The new research helps define the contributions of virus-neutralizing antibodies other than those directed at gp350 on B cells. Among other findings, the team determined that antibodies to viral proteins called the gH/gL complex play a major role in inhibiting EBV fusion with epithelial cells.
A cryo-EM image of the gH/gL/gp45 candidate vaccine construct.
Tuesday, April 9, 2019
Young children who live close to a major roadway are twice as likely to score lower on tests of communications skills, compared to those who live farther away from a major roadway, according to an analysis by researchers at the National Institutes of Health and the University of California, Merced. Moreover, children born to women exposed during pregnancy to higher-than-normal levels of traffic-related pollutants — ultra-fine airborne particles and ozone — had a small but significantly higher likelihood of developmental delays during infancy and early childhood. The study appears in Environmental Research.
“Our results suggest that it may be prudent to minimize exposure to air pollution during pregnancy, infancy, and early childhood — all key periods for brain development,” said Pauline Mendola, Ph.D., an investigator in the Division of Intramural Population Health Research at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the study’s senior author.
Previous studies have linked exposure to common air pollutants in pregnancy to low birthweight, preterm birth and stillbirth. A few studies have found a higher risk of autism and of lower cognitive functioning in children living near freeways, but results of studies about how prenatal and early childhood exposure to air pollution might affect development have been inconsistent.
Wednesday, April 3, 2019
Small IRP clinical trial conducted in partnership with AstraZeneca
A drug approved to treat a severe form of asthma dramatically improved the health of people with rare chronic immune disorders called hypereosinophilic syndromes (HES) in whom other treatments were ineffective or intolerable. This finding comes from a small clinical trial led by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and conducted through a partnership with the global biopharmaceutical company AstraZeneca. The results were published online today in the New England Journal of Medicine.
“People living with a rare disease often have few, if any, effective treatment options,” said NIAID Director Anthony S. Fauci, M.D. “This promising treatment advance for people with hypereosinophilic syndromes is just one example of how NIH research responds to the unique medical needs of individuals with rare diseases.”
HES is caused by higher-than-normal numbers of white blood cells called eosinophils in the blood, tissues or both. While most people have 0 to 500 eosinophils per microliter (µL) of blood, people with HES typically have more than 1,500 eosinophils/µL. The symptoms of HES vary widely from one patient to the next and can affect the heart, lungs, skin, gastrointestinal tract, central nervous system and other organ systems.
Activated eosinophils in the peripheral blood of a patient with idiopathic hypereosinophilic syndrome.
Wednesday, April 3, 2019
Investigational vaccine designed to provide broad, durable protection from flu
The first clinical trial of an innovative universal influenza vaccine candidate is examining the vaccine’s safety and tolerability as well as its ability to induce an immune response in healthy volunteers. Scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, developed the experimental vaccine, known as H1ssF_3928.
H1ssF_3928 is designed to teach the body to make protective immune responses against diverse influenza subtypes by focusing the immune system on a portion of the virus that varies relatively little from strain to strain. The vaccine candidate was developed as part of a broader research agenda to create a so-called “universal” influenza vaccine that can provide long-lasting protection for all age groups from multiple influenza subtypes, including those that might cause a pandemic.
“Seasonal influenza is a perpetual public health challenge, and we continually face the possibility of an influenza pandemic resulting from the emergence and spread of novel influenza viruses,” said NIAID Director Anthony S. Fauci, M.D. “This Phase 1 clinical trial is a step forward in our efforts to develop a durable and broadly protective universal influenza vaccine.”
A healthy volunteer receives an experimental universal influenza vaccine known as H1ssF_3928 as part of a Phase 1 clinical trial at the NIH Clinical Center in Bethesda, Maryland. Scientists at NIAID’s Vaccine Research Center (VRC) developed the vaccine.
Tuesday, April 2, 2019
The drug colchicine, used to treat the arthritic condition gout, could potentially reduce complications accompanying metabolic syndrome, a combination of high blood pressure, high blood sugar and other conditions that increase the risk of heart disease and type 2 diabetes, according to researchers at the National Institutes of Health. Their study appears in Diabetes, Endocrinology, and Metabolism.
Previous studies have indicated that the system-wide inflammation that occurs in obesity plays a role in the development of type 2 diabetes. In the current study, researchers led by Jack A. Yanovski, M.D., Ph.D., of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) randomly assigned 21 study participants to received colchicine twice a day for three months, while 19 participants received a placebo. Colchicine suppresses a multi-protein complex called NLRP3, which triggers the inflammation seen in obesity.
Researchers looked at several measures that reflect how well insulin works in the body to clear sugar from the blood (insulin resistance). There was no difference between the two groups in insulin resistance determined by one measure of insulin use (the frequently sampled, insulin-modified intravenous glucose tolerance test). However, the colchicine group showed improvement on the Homeostatic Model Assessment of Insulin Resistance test, which also estimates how much insulin is needed to keep blood sugar at a normal level while fasting. Those in the colchicine group also scored lower on a blood test of C-reactive protein and other tests that indicate inflammation. The authors concluded that larger studies are needed to determine if colchicine could prevent the development of type 2 diabetes in people with metabolic syndrome.
Thursday, March 28, 2019
A new study led by scientists in the Center for Cancer Research (CCR) at the National Cancer Institute (NCI) sheds light on one way tumors may continue to grow despite the presence of cancer-killing immune cells. The findings, published March 29, 2019, in Science, suggest a way to enhance the effectiveness of immunotherapies for cancer treatment. NCI is part of the National Institutes of Health.
Dying cancer cells release the chemical potassium, which can reach high levels in some tumors. The research team reported that elevated potassium causes T cells to maintain a stem-cell-like quality, or “stemness,” that is closely tied to their ability to eliminate cancer during immunotherapy. The findings suggest that increasing T cells’ exposure to potassium — or mimicking the effects of high potassium — could make cancer immunotherapies more effective.
“This study helps us better understand why cancer immunotherapy works the way it does,” said Nicholas Restifo, M.D., of NCI’s CCR, who led the research team. “It could also point the way toward generating better and more long-lasting responses to these treatments.”
Wednesday, March 27, 2019
Microglia may benefit, not damage, photoreceptors
National Institutes of Health scientists studying the progression of inherited and infectious eye diseases that can cause blindness have found that microglia, a type of nervous system cell suspected to cause retinal damage, surprisingly had no damaging role during prion disease in mice. In contrast, the study findings indicated that microglia might delay disease progression.
The discovery could apply to studies of inherited photoreceptor degeneration diseases in people, known as retinitis pigmentosa. In retinitis pigmentosa cases, scientists find an influx of microglia near the photoreceptors, which led to the belief that microglia contribute to retina damage.
These inherited diseases appear to damage the retina similarly to prion diseases. Prion diseases are slow degenerative diseases of the central nervous system that occur in people and various other mammals. No vaccines or treatments are available, and the diseases are almost always fatal. Prion diseases primarily involve the brain but also can affect the retina and other tissues.
Microglia have been shown to be beneficial in slowing prion disease progression in the brain, and now in retina. Microglial cells (green) are engulfing and eliminating prion-damaged photoreceptors (red), which appears to slow retinal degeneration.
Thursday, March 21, 2019
Technique could aid early detection and treatment of certain eye diseases
Cells of the retinal pigment epithelium (RPE) form unique patterns that can be used to track changes in this important layer of tissue in the back of the eye, researchers at the National Eye Institute (NEI) have found. Using a combination of adaptive optics imaging and a fluorescent dye, the researchers used the RPE patterns to track individual cells in healthy volunteers and people with retinal disease. The new finding could provide a way to study the progression and treatment of blinding diseases that affect the RPE. The study was published today in the journal JCI Insight. NEI is part of the National Institutes of Health (NIH).
“Studying cells of the retinal pigment epithelium in the clinic is like looking into a black box. RPE cells are difficult to see, and by the time signs of disease are detectable with conventional techniques, a lot of damage has often already occurred,” said Johnny Tam, Ph.D., the lead author of the study. “This study is proof-of-concept that we can use a fluorescent dye to reveal this unique fingerprint of the RPE, and to monitor the tissue over time.”
Mosaic of retinal pigment epithelial cells.
Thursday, March 21, 2019
People taking the mineral for other medical reasons should stay the course
Eating a calcium-rich diet or taking calcium supplements does not appear to increase the risk of age-related macular degeneration (AMD), according to the findings of a study by scientists at the National Eye Institute (NEI). AMD is a leading cause of vision loss and blindness among people age 65 and older in the United States. The study findings are published in JAMA Ophthalmology.
The findings contradict an earlier study indicating that high levels of calcium were associated with increased prevalence of AMD, but they are consistent with another suggesting that calcium has a protective role in AMD.
“Although the findings suggest that high calcium intake may be protective, the jury is still out on whether people should alter their calcium intake to prevent the onset or progression of AMD,” said the study’s lead investigator, Emily Chew, M.D., director of the Division of Epidemiology and Clinical Applications and the deputy clinical director at NEI, which is part of the National Institutes of Health.
Calcium-rich foods include milk, yogurt and cheese, as well as non-dairy sources such as kale, white beans and sesame seeds.
Wednesday, March 20, 2019
Approximately 1 in 9 women in the United States experiences symptoms of postpartum depression, according to the Centers for Disease Control and Prevention. Now, the U. S. Food and Drug Administration (FDA) has approved brexanolone, an analog of the endogenous human hormone allopregnanolone and the first drug specifically designed to treat postpartum depression.
Some psychiatric drugs owe their discovery to chance — serendipitous observations of clinical benefit — or a process of incremental improvement based on drugs previously discovered by chance. Not so with brexanolone, which has a truly novel mechanism of action and was developed by design, thanks to a series of basic and translational neuroscience studies. FDA approval represents the final phase of a bench-to-bedside journey for this drug — a journey that began in the NIMH Intramural Research Program (IRP).
In the 1980s, NIMH IRP researchers discovered that metabolites (products formed when the body breaks down or “metabolizes” other substances) of the steroid hormones progesterone and deoxycorticosterone bound to and acted upon receptors for gamma-aminobutyric acid (GABA) — a major inhibitory neurotransmitter in the brain. These steroids were found to amplify GABA-activated chloride ion currents, thereby impacting the excitability of neurons.