In the News

Study links gut-homing protein levels with HIV infection risk, disease progression

Wednesday, January 24, 2018

NIH clinical trial is testing antibody against the protein in people with HIV.

For the first time, scientists have shown a relationship between the proportion of key immune cells that display high levels of a gut-homing protein called alpha-4 beta-7 at the time of HIV infection and health outcomes. Previous research illustrated this relationship in monkeys infected with a simian form of HIV.

The new study found that women who had more CD4+ T cells displaying high levels of alpha-4 beta-7 on their surface were more likely to become infected with HIV, and the virus damaged their immune systems more rapidly, than women with fewer such cells. The National Institutes of Health co-funded the study with the South African Medical Research Council as part of the U.S.–South Africa Program for Collaborative Biomedical Research. In addition, NIH scientists collaborated on the study. The report appears online today in the journal Science Translational Medicine.

“Our findings suggest that having a high frequency of alpha-4 beta-7-expressing CD4+ T cells, which HIV preferentially infects, leads to more HIV-infected CD4+ T cells moving to the gut, which in turn leads to extensive damage to gut-based immune cells,” said Anthony S. Fauci, M.D. Dr. Fauci co-authored the paper as chief of the Laboratory of Immunoregulation at the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH. He also is director of NIAID.

Flu infection study increases understanding of natural immunity

Tuesday, January 23, 2018

Findings illustrate role of specific antibodies.

People with higher levels of antibodies against the stem portion of the influenza virus hemagglutinin (HA) protein have less viral shedding when they get the flu, but do not have fewer or less severe signs of illness, according to a new study published in mBio. HA sits on the surface of the influenza virus to help bind it to cells and features a head and stem region. Scientists only recently discovered that humans naturally generate anti-HA stem antibodies in response to flu infection, and this is the first study of its kind to evaluate pre-existing levels of these specific antibodies as a predictor of protection against influenza. The findings could have implications for flu vaccine development, according to the authors. Scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, conducted the research.

The study team has explored immune responses to two influenza surface proteins: HA—the main target of traditional seasonal flu vaccines—and neuraminidase (NA). The head region of HA is constantly changing, which is why influenza vaccine strains must be updated each year. The HA stem region, however, is less susceptible to change, making it a potential target for novel vaccines aimed at broader, more durable protection.

In the new analysis, investigators sought to understand the role of pre-existing anti-HA stem antibodies in protection against influenza using data from a healthy volunteer influenza challenge trial that took place in 2013 at the NIH Clinical Center in Bethesda, Maryland. Led by NIAID’s Matthew J. Memoli, M.D., the trial enrolled 65 healthy volunteers aged 18 to 50 years. Participants stayed in a specially designed isolation and infection control unit throughout the study. Investigators measured participants’ baseline levels of anti-HA stem antibodies, infected them with a 2009 H1N1 influenza virus, and then measured levels of anti-HA stem antibodies again.

NIH IRP scientists find microbes on the skin of mice promote tissue healing, immunity

Thursday, January 18, 2018

Insights may inform wound management techniques.

Beneficial bacteria on the skin of lab mice work with the animals’ immune systems to defend against disease-causing microbes and accelerate wound healing, according to new research from scientists at the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Researchers say untangling similar mechanisms in humans may improve approaches to managing skin wounds and treating other damaged tissues. The study was published online today in Cell.

Like humans and other mammals, mice are inhabited by large, diverse microbial populations collectively called the microbiome. While the microbiome is believed to have many beneficial functions across several organ systems, little is known about how the immune system responds to these harmless bacteria.

To investigate, NIAID scientists led by Yasmine Belkaid, Ph.D., chief of the Mucosal Immunology Section of NIAID’s Laboratory of Parasitic Diseases, observed the reaction of mouse immune cells to Staphylococcus epidermidis, a bacterium regularly found on human skin that does not normally cause disease. To their surprise, immune cells recognized S. epidermidis using evolutionarily ancient molecules called non-classical MHC molecules, which led to the production of unusual T cells with genes associated with tissue healing and antimicrobial defense. In contrast, immune cells recognize disease-causing bacteria with classical MHC molecules, which lead to the production of T cells that stoke inflammation.

Brian Berridge tapped to manage National Toxicology Program

Friday, January 12, 2018

NTP coordinates toxicology research and testing across nine different federal agencies.

The National Toxicology Program (NTP) has named Brian Berridge, D.V.M., Ph.D., as its new Associate Director. Berridge, formerly of GlaxoSmithKline, will oversee day-to-day operations as NTP coordinates toxicology research and testing across nine different federal agencies, including the National Institutes of Health, the U.S. Food and Drug Administration, and the Centers for Disease Control and Prevention. Berridge is replacing John Bucher, Ph.D., who has served as Associate Director since 2007 and plans to continue with NTP as a senior scientist.

Berridge will take over guidance of NTP products like the congressionally mandated Report on Carcinogens, which currently lists 248 cancer-causing agents, and scientific literature reviews on topics like fluoride that are nominated to NTP by other agencies or the public. He will also help oversee toxicological studies on topics such as chemical spills and cell phones. Since 1978, NTP has evaluated more than 2,800 chemicals and other agentsfor a variety of health-related effects, like contributing to cancer or being toxic to reproductive, immune, or nervous systems. NTP is headquartered at the National Institute of Environmental Health Sciences (NIEHS), part of NIH.

“We are thrilled that Dr. Berridge is bringing his expertise to environmental health, including experience with both traditional and novel toxicological methods,” said Linda Birnbaum, Ph.D., who has been the director of NTP since 2009, while also directing NIEHS. “We are also deeply appreciative of Dr. Bucher’s exemplary leadership for the past decade.”

The coming of age of gene therapy: A review of the past and path forward

Friday, January 12, 2018

No longer the future of medicine, gene therapy is part of present-day clinical treatment.

After three decades of hopes tempered by setbacks, gene therapy—the process of treating a disease by modifying a person’s DNA—is no longer the future of medicine, but is part of the present-day clinical treatment toolkit. The Jan. 12 issue of the journal Science provides an in-depth and timely review of the key developments that have led to several successful gene therapy treatments for patients with serious medical conditions.

Co-authored by Cynthia E. Dunbar, M.D., senior investigator at the Hematology Branch of the National Heart, Lung and Blood Institute (NHLBI), part of the National Institutes of Health, the article also discusses emerging genome editing technologies. According to Dunbar and her colleagues, these methods, including the CRISPR/Cas9 approach, would provide ways to correct or alter an individual's genome with precision, which should translate into broader and more effective gene therapy approaches.

Gene therapy is designed to introduce genetic material into cells to compensate for or correct abnormal genes. If a mutated gene causes damage to or spurs the disappearance of a necessary protein, for example, gene therapy may be able to introduce a normal copy of the gene to restore the function of that protein.

Iodine deficiency may reduce pregnancy chances, NIH study suggests

Thursday, January 11, 2018

Women with moderate to severe iodine deficiency may take longer to achieve a pregnancy, compared to women with normal iodine levels, according to a study by researchers at the National Institutes of Health. The study is the first to investigate the potential effects of mild to moderate iodine deficiency — common among women in the United States and the United Kingdom — on the ability to become pregnant. It appears in the latest edition of Human Reproduction.

Iodine is a mineral used by the body to regulate metabolism. It also helps regulate bone growth and brain development in children. It is found in seafood, iodized salt, dairy products, and some fruits and vegetables. Severe iodine deficiency has long been known to cause intellectual and developmental delays in infants.

“Our findings suggest that women who are thinking of becoming pregnant may need more iodine,” said James L. Mills, M.D., who conducted the study along with colleagues at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development and the New York State Department of Health in Albany. “Iodine requirements increase during pregnancy, and the fetus depends on this mineral to make thyroid hormone and to ensure normal brain development.”

NIH researchers report first 3D structure of DHHC enzymes

Thursday, January 11, 2018

Finding promises to improve drug design for common forms of cancer.

The first three-dimensional structure of DHHC proteins — enzymes involved in many cellular processes, including cancer — explains how they function and may offer a blueprint for designing therapeutic drugs. Researchers have proposed blocking DHHC activity to boost the effectiveness of first-line treatments against common forms of lung and breast cancer. However, there are currently no licensed drugs that target specific DHHC enzymes. The study, led by researchers at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), appears in the latest issue of Science. NICHD is part of the National Institutes of Health.

DHHC enzymes, also called palmitoyltransferases, modify other proteins by attaching to them a chain of lipids, or fatty acids, of varying lengths. This modification, called palmitoylation, can change many properties of a target protein, such as its structure, function and location within a cell. Researchers estimate that nearly 1,000 human proteins undergo palmitoylation, including epidermal growth factor receptors (EGFRs). A well-known EGFR is HER2, which is overactivated in aggressive forms of breast cancer. EGFRs can also be overactivated in colon cancer, and non-small cell lung cancer, the most common type of lung cancer.

The current study details the structures of a human DHHC enzyme, DHHC20, and the zebrafish version of another DHHC enzyme, DHHC15. Importantly, DHHC20 is the enzyme that palmitoylates EGFR. Previous studies have shown that blocking DHHC20 makes cancer cells more vulnerable to existing FDA-approved treatments that target EGFR. Therefore, understanding the structure of DHHC20 may be important for treating EGFR-driven cancers.

“Mutations in DHHC enzymes are associated with various cancers and neurological disorders,” according to Anirban Banerjee, Ph.D., the study’s lead author and head of NICHD’s Unit on Structural and Chemical Biology of Membrane Proteins. “Our study offers a starting point for developing DHHC20 inhibitors that may aid in treatment of common cancers and advance the field of protein palmitoylation.”

NIH study supports use of short-term HIV treatment interruption in clinical trials

Thursday, January 11, 2018

Findings may aid design of trials to assess strategies to control HIV without drugs.

A short-term pause in HIV treatment during a carefully monitored clinical trial does not lead to lasting expansion of the HIV reservoir nor cause irreversible damage to the immune system, new findings suggest.

Antiretroviral therapy (ART) benefits the health of people living with HIV, prolongs their lives and prevents transmission of the virus to others. If taken daily as directed, ART can reduce viral load — the amount of HIV in the blood — to levels that are undetectable with standard tests. However, the virus remains dormant in a small number of immune cells, and people living with HIV must take ART daily to keep the virus suppressed. If a person with ART-suppressed HIV stops taking medication, viral load will almost invariably rebound to high levels.

Researchers are working to develop therapeutic strategies to induce sustained ART-free remission — the absence of viral rebound following discontinuation of ART. Clinical trials to assess the efficacy of such experimental therapies may require participants to temporarily stop taking ART, an approach known as analytical treatment interruption, or ATI.

MERS antibodies produced in cattle safe, treatment well tolerated in Phase 1 trial

Wednesday, January 10, 2018

An experimental treatment developed from cattle plasma for Middle East respiratory syndrome (MERS) coronavirus infection shows broad potential, according to a small clinical trial led by National Institutes of Health scientists and their colleagues. The treatment, SAB-301, was safe and well tolerated by healthy volunteers, with only minor reactions documented.

The first confirmed case of MERS was reported in Saudi Arabia in 2012. Since then, the MERS coronavirus has spread to 27 countries and sickened more than 2,000 people, of whom about 35 percent have died, according to the World Health Organization. There are no licensed treatments for MERS.

SAB-301 was developed by SAB Biotherapeutics of Sioux Falls, South Dakota, and has been successfully tested in mice. The treatment comes from so-called “transchromosomic cattle.” These cattle have genes that have been slightly altered to enable them to produce fully human antibodies instead of cow antibodies against killed microbes with which they have been vaccinated — in this case the MERS virus. The clinical trial, conducted by NIH’s National Institute of Allergy and Infectious Diseases, took place at the NIH Clinical Center.

NIH discovery brings stem cell therapy for eye disease closer to the clinic

Tuesday, January 2, 2018

Stem cell-derived retinal cells need primary cilia to support survival of light-sensing photoreceptors.

Scientists at the National Eye Institute (NEI), part of the National Institutes of Health, report that tiny tube-like protrusions called primary cilia on cells of the retinal pigment epithelium (RPE) — a layer of cells in the back of the eye — are essential for the survival of the retina’s light-sensing photoreceptors. The discovery has advanced efforts to make stem cell-derived RPE for transplantation into patients with geographic atrophy, otherwise known as dry age-related macular degeneration (AMD), a leading cause of blindness in the U.S. The study appears in the January 2 Cell Reports.

“We now have a better idea about how to generate and replace RPE cells, which appear to be among the first type of cells to stop working properly in AMD,” said the study’s lead investigator, Kapil Bharti, Ph.D., Stadtman Investigator at the NEI. Bharti is leading the development of patient stem cell-derived RPE for an AMD clinical trial set to launch in 2018.

In a healthy eye, RPE cells nourish and support photoreceptors, the cells that convert light into electrical signals that travel to the brain via the optic nerve. RPE cells form a layer just behind the photoreceptors. In geographic atrophy, RPE cells die, which causes photoreceptors to degenerate, leading to vision loss.