Health
Researchers at the University of Georgia have discovered that a virus commonly found in dogs may serve as the foundation for the next great breakthrough in human vaccine development.
Although harmless in humans, parainfluenza virus 5, or PIV5, is thought to contribute to upper respiratory infections in dogs, and it is a common target for canine vaccines designed to prevent kennel cough. In a paper published recently in PLOS ONE, researchers describe how this virus could be used in humans to protect against diseases that have eluded vaccine efforts for decades.
“We can use this virus as a vector for all kinds of pathogens that are difficult to vaccinate against,” said Biao He, the study’s principal investigator and professor of infectious diseases in UGA’s College of Veterinary Medicine. “We have developed a very strong H5N1 flu vaccine with this technique, but we are also working on vaccines for HIV, tuberculosis and malaria.”
PIV5 does not cause disease in humans, as our immune system is able to recognize and destroy it. By placing antigens from other viruses or parasites inside PIV5, it effectively becomes a delivery vehicle that exposes the human immune system to important pathogens and allows it to create the antibodies that will protect against future infection.
This approach not only ensures full exposure to the vaccine but also is much safer because it does not require the use of attenuated, or weakened, pathogens. For example, an HIV vaccine delivered by PIV5 would contain only those parts of the HIV virus necessary to create immunity, making it impossible to contract the disease from the vaccine.
“Safety is always our number one concern,” said He, who is also a Georgia Research Alliance distinguished investigator and member of the Faculty of Infectious Diseases. “PIV5 makes it much easier to vaccinate without having to use live pathogens.”
Using viruses as a delivery mechanism for vaccines is not a new technique, but previous efforts have been fraught with difficulty. If humans or animals already possess a strong immunity to the virus used for delivery, the vaccine is unlikely to work, as it will be destroyed by the immune system too quickly.
“Pre-existing immunity to viruses is the main reason most of these vaccines fail,” He said.
But in this latest study, He and his colleagues demonstrate that immunity to PIV5 does not limit its effectiveness as a vaccine delivery mechanism, even though many animals–including humans– already carry antibodies against it.
In their experiments, the researchers found that a single dose inoculation using PIV5 protected mice from the influenza strain that causes seasonal flu. Another single dose experimental vaccine also protected mice from the highly pathogenic and deadly H5N1 virus commonly known as bird flu.
This recent work is a culmination of more than fifteen years of research and experimentation with the PIV5 virus, and He has confidence that it will serve as an excellent foundation for vaccines to treat diseases in both animals and humans.
“I believe we have the best H5N1 vaccine candidate in existence,” He said. “But we have also opened up a big field for a host of new vaccines.”
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An active lifestyle helps preserve gray matter in the brains of older adults and could reduce the burden of dementia and Alzheimer’s disease (AD), according to a study presented today at the annual meeting of the Radiological Society of North America (RSNA).
Dementia exacts a staggering toll on society. More than 35 million people worldwide are living with the disease, according to the World Health Organization, and the prevalence is expected to double by 2030. AD is the most common cause of dementia and currently has no cure.
Cyrus Raji, M.D., Ph.D., radiology resident at the University of California in Los Angeles, and colleagues recently examined how an active lifestyle can influence brain structure in 876 adults, average age 78 years, drawn from the multisite Cardiovascular Health Study. The patients’ condition ranged from normal cognition to Alzheimer’s dementia.
“We had 20 years of clinical data on this group, including body mass index and lifestyle habits,” Dr. Raji said. “We drew our patients from four sites across the country, and we were able to assess energy output in the form of kilocalories per week.”
The lifestyle factors examined included recreational sports, gardening and yard work, bicycling, dancing and riding an exercise cycle.
The researchers used magnetic resonance imaging (MRI) and a technique called voxel-based morphometry to model the relationships between energy output and gray matter volume.
“Voxel-based morphometry is an advanced method that allows a computer to analyze an MR image and build a mathematical model that helps us to understand the relationship between active lifestyle and gray matter volume,” Dr. Raji said. “Gray matter volume is a key marker of brain health. Larger gray matter volume means a healthier brain. Shrinking volume is seen in Alzheimer’s disease.”
After controlling for age, head size, cognitive impairment, gender, body mass index, education, study site location and white matter disease, the researchers found a strong association between energy output and gray matter volumes in areas of the brain crucial for cognitive function.
Greater caloric expenditure was related to larger gray matter volumes in the frontal, temporal and parietal lobes, including the hippocampus, posterior cingulate and basal ganglia.
There was a strong association between high energy output and greater gray matter volume in patients with mild cognitive impairment and AD.
“Gray matter includes neurons that function in cognition and higher order cognitive processes,” Dr. Raji said. “The areas of the brain that benefited from an active lifestyle are the ones that consume the most energy and are very sensitive to damage.”
A key aspect of the study was its focus on having variety in lifestyle choices, Dr. Raji noted.
“What struck me most about the study results is that it is not one but a combination of lifestyle choices and activities that benefit the brain,” he said.
Dr. Raji said the positive influence of an active lifestyle on the brain was likely due to improved vascular health.
“Virtually all of the physical activities examined in this study are some variation of aerobic physical activity, which we know from other work can improve cerebral blood flow and strengthen neuronal connections,” he said.
“Additional work needs to be done,” Dr. Raji added. “However, our initial results show that brain aging can be alleviated through an active lifestyle.”
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