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November 2, 2018
Digest
Scientists Develop Novel Vaccine for Lassa Fever, Rabies

A vaccine designed to protect people from both Lassa fever and rabies showed promise in preclinical testing.
A vaccine designed to protect people from both Lassa fever and rabies showed promise in preclinical testing.

PHOTO: NIAID

A novel vaccine designed to protect people from both Lassa fever and rabies showed promise in preclinical testing, according to new research published in Nature Communications. The investigational vaccine, called LASSARAB, was developed and tested by scientists at Thomas Jefferson University in Philadelphia; the University of Minho in Braga, Portugal; the University of California, San Diego; and NIAID.

The inactivated recombinant vaccine candidate uses a weakened rabies virus vector, or carrier. The research team inserted genetic material from Lassa virus into the rabies virus vector so the vaccine expresses surface proteins from both the Lassa virus and the rabies virus. These surface proteins prompt an immune response against both Lassa and rabies viruses. The recombinant vaccine was then inactivated to “kill” the live rabies virus used to make the carrier.

There are currently no approved Lassa fever vaccines. Although Lassa fever is often a mild illness, some people experience serious symptoms, such as hemorrhage (severe bleeding) and shock. The overall Lassa virus infection case-fatality rate is about 1 percent, according to the World Health Organization, but that rate rises to 15 percent for patients hospitalized with severe cases of Lassa fever.

People contract Lassa virus through contact with infected Mastomys rats and through exposure to an infected person’s bodily fluids. Lassa fever is endemic to West Africa where these rats are common. In 2018, Nigeria experienced its largest-ever Lassa fever outbreak, with 514 confirmed cases and 134 deaths from Jan. 1 through Sept. 30, according to the Nigeria Centre for Disease Control.  

Africa is also at high risk for human rabies. The WHO estimates that 95 percent of the estimated 59,000 human rabies death per year occur in Africa and Asia. Nearly all human rabies deaths are caused by bites or scratches from infected dogs. Effective rabies vaccines and post-exposure shots are available, but many deaths still occur in resource-limited countries, according to the Centers for Disease Control and Prevention.

Study Identifies Gene That Makes Gentle Touch Feel Painful after Injury

NIH researchers found that a gene previously shown to control our sense of our bodies in space may also be responsible for tactile allodynia, the skin’s reaction to injury that makes normally gentle touches feel painful.
NIH researchers found that a gene previously shown to control our sense of our bodies in space may also be responsible for tactile allodynia, the skin’s reaction to injury that makes normally gentle touches feel painful.

IMAGE: STEVE DEBENPORT/GETTY

Ever wonder why things that normally feel gentle, like putting on soft shirts, are painful after a sunburn? In a study of 4 patients with a rare genetic disorder, NIH researchers found that PIEZO2, a gene previously shown to control our sense of our bodies in space and gentle touch, may also be responsible for tactile allodynia: the skin’s reaction to injury that makes normally gentle touches feel painful.

This and a second NIH-funded study, both published in Science Translational Medicine, used mice to show how the gene may play an essential role in the nervous system’s reaction to injury and inflammation, making PIEZO2 a target for developing precise treatments for relieving the pain caused by cuts, burns and other skin injuries.

“For years scientists have been trying to solve the mystery of how gentle touch becomes painful,” said Dr. Alexander Chesler, a Stadtman investigator at NCCIH and a senior author of one of the studies. “These results suggest PIEZO2 is the gene for tactile allodynia. We hope that these results will help researchers develop better treatments for managing this form of pain.”

The PIEZO2 gene encodes what scientists call a mechanosensitive protein that produces electrical nerve signals in response to changes in cell shape, such as when skin cells and neurons of the hand are pressed against a table. Since its discovery in mice by a team led by Dr. Ardem Patapoutian of Scripps Research, La Jolla, the lead author of the second paper, scientists have proposed that PIEZO2 plays an important role in touch and pain in humans.

Gene Mutation Points to New Way to Fight Diabetes, Obesity, Heart Disease

Researchers say they have discovered a gene mutation that slows the metabolism of sugar in the gut, giving people who have the mutation a distinct advantage over those who do not. Those with the mutation have a lower risk of diabetes, obesity, heart failure and even death. The researchers say their finding could provide the basis for drug therapies that could mimic the workings of this gene mutation, offering a potential benefit for the millions of people who suffer with diabetes, heart disease and obesity.  

The study, which is largely supported by NHLBI, appeared in the Journal of the American College of Cardiology.  

“We’re excited about this study because it helps clarify the link between what we eat, what we absorb and our risk for disease. Knowing this opens the door to improved therapies for cardiometabolic disease,” said Dr. Scott D. Solomon, a professor of medicine at Harvard Medical School and a senior physician at Brigham and Women’s Hospital in Boston, who led the research. He explained that the study is the first to fully evaluate the link between mutations in the gene mainly responsible for absorbing glucose in the gut—SGLT-1, or sodium glucose co-transporter-1—and cardiometabolic disease.

People who have the natural gene mutation appear to have an advantage when it comes to diet, Solomon noted. Those who eat a high-carbohydrate diet and have this mutation will absorb less glucose than those without the mutation. A high-carbohydrate diet includes such foods as pasta, breads, cookies and sugar-sweetened beverages.

In the study, the researchers analyzed the relationship between SGLT-1 mutations and cardiometabolic disease using genetic data obtained from 8,478 participants in the Atherosclerosis Risk in Communities (ARIC) study. The study was a 25-year-long observational trial of atherosclerosis and cardiovascular risk factors in people living in four U.S. communities.

The researchers found that about 6 percent of the subjects carried a mutation in SGLT-1 that causes limited impairment of glucose absorption. Individuals with this mutation had a lower incidence of type 2 diabetes, were less obese, had a lower incidence of heart failure, and had a lower mortality rate when compared to those without the mutation, even after adjusting for dietary intake (including total calories, sodium, and sugars). 

Based on these findings, the scientists suggest that selectively blocking the SGLT-1 receptor could provide a way to slow down glucose uptake to prevent or treat cardiometabolic disease and its consequences.

They caution that development of such targeted drugs could take years and that clinical trials are still needed to determine if the drugs reduce the incidence of diabetes and heart failure and improve lifespan.

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