‪‪National Institutes of Health‬‬

NIH begins study of vaccine to protect against mosquito-borne diseases

The National Institute of Allergy and Infectious Diseases (NIAID)

News Release

Tuesday, February 21, 2017

Experimental vaccine targets mosquito saliva.

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has launched a Phase 1 clinical trial to test an investigational vaccine intended to provide broad protection against a range of mosquito-transmitted diseases, such as Zika, malaria, West Nile fever and dengue fever, and to hinder the ability of mosquitoes to transmit such infections. The study, which is being conducted at the NIH Clinical Center in Bethesda, Maryland, will examine the experimental vaccine’s safety and ability to generate an immune response.

The investigational vaccine, called AGS-v, was developed by the London-based pharmaceutical company SEEK, which has since formed a joint venture with hVIVO in London. The consulting group Halloran has provided regulatory advice to both companies.

Unlike other vaccines targeting specific mosquito-borne diseases, the AGS-v candidate is designed to trigger an immune response to mosquito saliva rather than to a specific virus or parasite carried by mosquitoes. The test vaccine contains four synthetic proteins from mosquito salivary glands. The proteins are designed to induce antibodies in a vaccinated individual and to cause a modified allergic response that can prevent infection when a person is bitten by a disease-carrying mosquito.

“Mosquitoes cause more human disease and death than any other animal,” said NIAID Director Anthony S. Fauci, M.D. “A single vaccine capable of protecting against the scourge of mosquito-borne diseases is a novel concept that, if proven successful, would be a monumental public health advance.”

Led by Matthew J. Memoli, M.D., director of the Clinical Studies Unit in NIAID’s Laboratory of Infectious Diseases, the clinical trial is expected to enrol up to 60 healthy adults ages 18 to 50 years. Participants will be randomly assigned to receive one of three vaccine regimens. The first group will receive two injections of the AGS-v vaccine, 21 days apart. The second group will receive two injections of AGS-v combined with an adjuvant, 21 days apart. The adjuvant is an oil and water mixture commonly added to vaccines to enhance immune responses. The third group will receive two placebo injections of sterile water 21 days apart. Neither the study investigators nor the participants will know who is assigned to each group.

Participants will be asked to return to the clinic twice between vaccinations and twice after the second vaccination to undergo a physical exam and to provide blood samples. Study investigators will examine the blood samples to measure levels of antibodies triggered by vaccination.

Each participant also will return to the Clinical Center approximately 21 days after completing the vaccination schedule to undergo a controlled exposure to biting mosquitoes. The mosquitoes will not be carrying viruses or parasites, so the participants are not at risk of becoming infected with a mosquito-borne disease. Five to 10 female Aedes aegypti mosquitoes from the insectary in NIAID’s Laboratory of Malaria and Vector Research will be put in a feeding device that will be placed on each participant’s arm for 20 minutes. The mosquitoes will bite the participants’ arms through the netting on the feeding devices.

Afterwards, investigators will take blood samples from each participant at various time points to see if participants experience a modified response to the mosquito bites as a result of AGS-v vaccination.

Investigators also will examine the mosquitoes after the feeding to assess any changes to their life cycle. Scientists suspect that the mosquitoes who take a blood meal from ASG-v-vaccinated participants may have altered behaviour that could lead to early death or a reduced ability to reproduce. This would indicate that the experimental vaccine could also hinder disease transmission by controlling the mosquito population.

All participants will be asked to return to the clinic for follow-up visits every 60 days for five months following the mosquito feeding. A final clinic visit to assess long-term safety will take place approximately 10 months after the mosquito feeding. Throughout the trial, an independent Data and Safety Monitoring Board will review study data to evaluate participant safety and the overall conduct of the study. A medical monitor from NIAID’s Office of Clinical Research Policy and Regulatory Operations will also perform routine safety assessments.

The study is expected to be completed by summer 2018. For more information about the trial, see clinicaltrials.gov using the trial identifier NCT03055000.

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centres and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health®

To take care of your heart, even little changes can help

Eat better, drink less, exercise more, sleep enough: It's common advice for heart health - and it's frequently ignored. Just 3 percent of American adults meet the standards for healthy levels of physical activity, consumption of fruit and vegetables, body fat and smoking, according to the recent study.

But a major lifestyle overhaul isn't the only way to help your heart, studies suggest. Even small changes can make substantial differences.

Eventually, little changes can add up, says David Goff, director of the cardiovascular sciences division at the National Heart, Lung, and Blood Institute in Bethesda.


"Any small change you make in a positive direction is good for you," he says. "It's not an all-or-nothing phenomenon."

Physical activity is a perfect example, Goff says. Official guidelines, which recommend 30 minutes of moderately intense activity on most days, are based partly on evidence of substantial health benefits from doing 150 to 300 minutes of exercise each week, according to a 2011 review study by researchers at the University of South Carolina at Columbia. Those benefits include reduced risks of coronary heart disease, stroke and high blood pressure.

But the guidelines also come out of an assessment of what is obtainable for most people, Goff adds. And while it would be ideal to get at least 150 minutes of exercise weekly, getting less than that also has benefits. When the researchers looked at deaths from all causes, they saw the sharpest drop in mortality when exercise jumped from half an hour to an hour and a half each week.

Just getting up for a minute or two to interrupt bouts of sitting may also improve health, the study noted. And moving for as little as eight minutes a few times a day provides the same cardiovascular benefits as 30 uninterrupted minutes.

"If you can't find 30 minutes a day, try to find five or 10 or 15," Goff says. "Anything is better than nothing."

The "some are better than none" philosophy applies to dietary improvements, too, Goff says. According to the National Institutes of Health, an ideal meal plan includes lots of fruit, vegetables and whole grains, with limited amounts of fatty meat and tropical oils.

But eating an imperfect diet with more of the good stuff is better than giving up entirely. That's a conclusion from a 2016 study that created food-quality scores from the self-reported diets of about 200,000 people. Over about 25 years, the study found, people whose diets scored lowest had a 13 percent higher risk of coronary artery disease than did people in the second-worst group.

Even just switching out soda and other sugar-sweetened beverages can help eliminate a couple hundred calories a day and control weight. That helps lower blood pressure, levels of harmful cholesterol and the potential for diabetes - all risk factors for heart disease, Goff says. Large long-term studies have shown that people who average one sugary drink a day have a 20 percent higher risk of heart attack than people who rarely drink any.

It's not just food and diet, adds Michael Miller, director of the Center for Preventive Cardiology at the University of Maryland School of Medicine in and author of "Heal Your Heart: The Positive Emotions Prescription to Prevent and Reverse Heart Disease." Heart strength can also come from battling stress by boosting emotional health in simple and unexpected ways, he says, such as enjoying a good laugh.

In a small 2005 study, Miller played movie clips for 20 people. When participants watched a scene that made them laugh, 19 of them experienced dilation of the blood vessels. In contrast, a stressful scene led to constriction in 14 of the 20 viewers. Since then, Miller says, other small studies have found similar results, including one showing that vessels stayed dilated for 24 hours. Dilation allows more blood to flow, decreasing blood pressure and heart rate.

"Cross-talk" between the brain and heart explains the potential long-term benefits of laughter, Miller says, particularly when laughter is intense enough to induce crying. Belly laughing releases endorphins, triggering receptors in blood vessels to produce nitric oxide, which in turn, dilates blood vessels, increases blood flow, reduces the risk of blood clots, and more.

People are far more likely to laugh when they're with friends, Miller adds, adding yet more evidence of the health benefits of being social.

Accumulating evidence suggests that another easy and enjoyable way to help your heart is to listen to music. During recovery from surgery, several studies have shown, listening to relaxing music leads to a reduction in anxiety and heart rate. And in a 2015 study, Greek researchers found reductions in how hard the hearts of 20 healthy young adults were working after 30 minutes of listening to rock or classical music.

"I tell my patients to dust off their old LPs now that LPs are coming back and listen to a piece of music they have not heard in a long time but in the past made them feel really good," Miller says.

Also on his list of recommendations: mindfulness meditation and hugging. Both, he says, look promising in studies of heart health and heart repair.

"Considering that stress probably accounts for a third of heart attacks," he says, "it can have a dramatic effect if you do all of these things in sync."

Small lifestyle change help at any age, suggests a 2014 study that started by assessing cardiovascular risks in more than 5,000 young adults in the mid-1980s. Twenty years later, people who had made even small but positive changes - such as losing a little weight, exercising a bit more or smoking a little less - showed less coronary artery calcification than people who didn't change or changed in a negative direction. Coronary artery calcification is a risk factor for heart disease.

For the best chance of success, Goff suggests taking on one little change at a time.

"The idea is to make a small change and then make another small change," he says. "It's about changing the way you live over years and years, not hours and days."

MSU graduate student receives more than $60,000 scholarship from National Institute of Environmental Health Sciences

February 14, 2017 -- By Evelyn Boswell for the MSU News Service

BOZEMAN — A Montana State University graduate student with a passion for serving his tribe has received another major scholarship to continue researching water quality on Montana's largest Indian reservation.

The plan is to combine his findings with others in a multi-institutional effort to reduce health risks on the Crow Reservation in south-central Montana.

"I'm grateful for it," Emery Three Irons said of the $67,390 scholarship he received from the National Institute of Environmental Health Sciences (NIEHS).

The two-year scholarship – the latest in a series of awards for Three Irons, a member of the Apsaalooke tribe – will allow Three Irons to investigate and analyse factors associated with coliform bacteria that contaminate home well water and how that relates to metals contamination.

"His results will help us to better mitigate home well water contamination and thus reduce health risks to the Crow Tribal community," said collaborator Mari Eggers, a research scientist in environmental health in MSU's Center for Biofilm Engineering.

Another collaborator, tribal elder John Doyle, said researchers and tribal leaders have long tried to understand the connection between water quality and health problems on the Crow Reservation.

"We have looked at nearly all sources of our water from wells to springs, our rivers and creeks and what contamination is present," Doyle said. "This broad look is what will help give direction as Emery and other young tribal members work to address them."

In his newly funded project, Three Irons will work most directly with Eggers, Doyle and other members of the Crow Water Quality Project based at Little Big Horn College.

"He is an outstanding student and scientist and is committed to using his expertise in geospatial and environmental science to benefit his tribe and community," Eggers said. "We are thrilled to be collaborating with both Emery and his adviser, Dr Scott Powell, on our Crow Water Quality Project."

Doyle said, "Emery has worked very hard to get where he is now. He is very connected to our Apsaalooke community and has made every effort to be fully aware of all the challenges that we need to address.

"What makes him stand out is his clear vision and willingness to step in and find solutions," Doyle continued "I can see his leadership ability and believe that will continue to develop with the knowledge he gains at MSU."

Eggers said Three Irons' research will supplement work being conducted through a $500,000 grant awarded last summer to MSU and Little Big Horn College. That award was the result of a collaboration with the University of New Mexico, which received a five-year, $5 million award to open a Center for Native American Health Equity Research (Native HE Equity).

UNM directors Johnnie Lewis and Melissa Gonzales said the major goal of the centre is to build a strong body of scientific data to understand how environmental contaminants affect Native American health.

"Correcting this gap in current research into the future requires building a long-term network of Native American scholars and peers," they said. "By supplementing Emery's research through the centre the NIEHS and the centre can help to build this network.

"This network also benefits the work of the centre by bringing Emery's interest in bacterial contamination of water together with the centre's work on metal contamination in water and our interest in exposures to metals in mine waste," the directors said.

"Bacteria in the environment can act much like bacteria in humans to change the chemical form of contaminants and thereby alter their toxicity," they explained. "Adding Emery's work to Native EH Equity will help us to understand how metals in water may be altered by bacteria and the ultimate impact on toxicity, while also broadening Emery's understanding of toxicology. Native EH Equity is very excited to have this opportunity to support such a promising new Native American scientist."

Three Irons earned his bachelor's degree in geospatial and environmental analysis from MSU in 2015. He is currently working on his master's degree in MSU's Department of  Land Resources and Environmental Sciences (LRES) in the College of Agriculture. Last fall, he was selected for a $20,000 scholarship from the A.P. Sloan Foundation and a $5,000 scholarship from the Montana Institute on Ecosystems. As an undergraduate, he received the prestigious Udall Scholarship from the Morris K. Udall and Stewart L. Udall Foundation.

"Emery is a very motivated, sincere individual," said Powell, Three Irons' adviser and an assistant professor in LRES. "This (new) grant will lay the foundation for his master's degree and position him well for future endeavours. He aspires to be the lead GIS/geospatial analyst for the Crow tribe and without a doubt, this grant and broader master's degree experience will set him up perfectly to be in a strong position to attain that role for his tribe.

"Moreover, the NIH grant will provide him with an even broader context of Native American science and research -- allowing him to establish contacts beyond MSU and Crow," Powell said. "He is a very worthy candidate for this grant and degree. He works extremely hard, and he is also very committed to his family and community in Crow."

Three Irons is married and the father of four children, the youngest born three days before the beginning of the 2017 spring semester. After he completes his degree, Three Irons said he will return to the Crow Reservation to serve his people. Water quality may be his first focus, but he can see himself branching off into other issues.

"He truly wants to help his community, and he is committed to his community," Powell said. "He is uniquely in a position to gain an education and tools that will help his community."

Three Irons' award was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under award number P50ES026102. The P50 award is jointly funded by NIEHS and the National Institute on Minority Health and Health Disparities of the NIH and the Environmental Protection Agency. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.


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