In the midst of the novel coronavirus (COVID-19) outbreak, scientists at the National Primate Research Centers (NPRCs) have initiated research programs to better understand and diagnose as well as develop potential treatments and vaccines for the disease. NPRC animal colonies will be key in moving SARS-CoV-2 infection/COVID-19 research from cell models to studies in whole living systems so researchers can determine treatment safety and effectiveness.

Since the virus began to spread at the end of 2019, more than 3 million people have been infected worldwide as of April 28, 2020, with numbers growing daily. The coordinated efforts of the scientific community will be crucial to slow the spread of COVID-19, lower the risk of transmission and treat those who have the disease.

NPRC COVID-19 Research

Several of the NPRCs have made public announcements that research is under way, including California NPRC, Southwest NPRC, Tulane NPRC and Wisconsin NPRC. Others, including Oregon, Washington and Yerkes NPRCs, are also beginning research, and Oregon and Yerkes are accepting applications for COVID-19 pilot projects, which facilitate research collaborations and provide important preliminary data.

California NPRC researchers have already isolated, characterized and cultured COVID-19 from a patient treated at UC Davis, the first community-acquired case in the U.S. Next, they plan to make diagnostic tests in-house.

The Southwest NPRC scientists are proposing research projects to establish a nonhuman primate model to study the development and transmission of the disease, test new detection methods and partner with others in the scientific community.

At Tulane NPRC, researchers plan to create a nonhuman primate model to study the disease’s clinical progression, how it is transmitted through the air and how it specifically affects aging populations. The scientists are aiming to answer many questions, including why older individuals are more susceptible to complications and death from COVID-19.

In Wisconsin NPRC researchers have developed a coalition of scientists to combat the disease, drawing heavily from their firsthand experience during the Zika virus outbreak in 2016.

Yerkes NPRC researchers have begun initial research, and the center’s goals include understanding immunity and antibody response to SARS-CoV-2, and developing diagnostics, key reagents, antiviral therapies and vaccines.

COVID-19 Research Safety

The NPRCs are well-positioned to conduct SARS-CoV-2 infection/COVID-19 research because of our expertise in infectious diseases and collaborations internally at each NPRC as well as across NPRCs and with colleagues worldwide. Also, we can conduct such research safely in our Biosafety Level 3 (BSL3) facilities specifically designed to keep personnel, the research and the environment safe. Examples of BSL3 safety features include additional training and oversight for employees, directional air flow and filtered ventilation systems, and specialty equipment to contain the virus isolates used in the research and to decontaminate the lab space and research equipment and supplies.

News Stories about NPRC COVID-19 Research

Recent news articles by STAT News, Bloomberg, The Scientist and ABC News provide more information about the NPRC studies and the critical role of research with animals.

As we have more information to share about NPRC COVID-19 research, we’ll post information at NPRC.org/news and tweet from @NPRCnews. In the meantime, here are a few helpful COVID-19 resources we’re following.

At the NPRCs, our focus is conducting research and caring for our irreplaceable animal colonies so we can help people and animals live healthier lives. In the midst of the global COVID-19 pandemic, we are prioritizing our research to focus on developing diagnostics, preventions and treatments for this novel disease.

As we work to combat this health crisis, we also want to help keep you informed about the latest developments. Below are some of the resources we are following. These organizations are on the front lines of combatting COVID-19 and are frequently sharing crucial information regarding public health, personal guidelines and coronavirus research.

Centers for Disease Control and Prevention (CDC)
https://www.cdc.gov/coronavirus/2019-ncov/index.html
https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html

World Health Organization
www.who.int/emergencies/diseases/novel-coronavirus-2019

National Institutes of Health
https://www.nih.gov/health-information/coronavirus

In addition, we want to provide resources to help address any mental health and emotional well-being concerns COVID-19 brings for you and your loved ones:

CDC’s Recommendations for Managing Anxiety and Stress
https://www.cdc.gov/coronavirus/2019-ncov/prepare/managing-stress-anxiety.html

National Alliance on Mental Illness
https://www.nami.org/About-NAMI/NAMI-News/2020/NAMI-Updates-on-the-Coronavirus

Just for Kids: A Comic Exploring the New Coronavirus
https://www.npr.org/sections/goatsandsoda/2020/02/28/809580453/just-for-kids-a-comic-exploring-the-new-coronavirus

The NPRCs are working closely with our collaborators worldwide to address COVID-19. Look for updates from us at NPRC.org and @NPRCnews.

You may want to think twice before sharing a bite of spare food with animals you encounter in public places. That is, unless you’re willing to risk a staph infection.

Staphylococcus aureus (S. aureus) is a bacterium that causes a wide range of infections, such as skin and soft tissue infections (SSTI), bone, joint and implant infections, pneumonia and more. Both penicillin and methicillin have been used to fight S. aureus, but strains resistant to all types of treatment have continued to emerge. Now, methicillin-resistant S. aureus (MRSA) has become a serious international problem.

In a hospital setting, MRSA can be deadly; in fact, it caused 11,000 deaths in hospitals in the U.S. in 2017. And while practices to reduce MRSA cases in hospital populations are improving, the bacterium continues to thrive in the wild in certain geographic areas. It is of particular concern in places where large numbers of humans and animals interact, including popular tourist destinations.

In a recent study, researchers at the Washington National Primate Research Center (WaNPRC) at the University of Washington (UW) along with their Nepali colleagues sampled 59 rhesus monkeys within Nepal. Those monkeys have close interactions with humans, usually at temple sites, where people offer the animals food. The researchers used a non-invasive method to collect saliva samples from the monkeys with subsequent processing at a microbiology laboratory in Nepal.

The findings were astounding. Of the macaque samples tested, 6.8% were positive for MRSA, and three of four MRSA isolates were identified as ST22 SCCmec IV. The ST22 SCCmec IV strain is normally considered a human strain, and this study suggests that humans in Nepal are sharing their strains with the wild macaque populations.

The researchers further reiterate a warning that is becoming all too well known, that even minimal contact with wild animals, especially contact with saliva or an animal bite can present significant health risks to humans.

“Some types of MRSA are found all over the world and are pandemic strains,” said lead study author Marilyn C. Roberts, PhD. “The importance should be stressed in respect to these populations of wild animals. Even feeding chipmunks or ducks human food is not a good thing. They can pick up what we have, and we can pick up what they have. Some of the infectious agents wildlife carry can be deadly.”

“Given the results of our work in Nepal, we are now extending the MRSA investigation to primates in Thailand. These efforts are part of our larger collaborative program promoting the healthy coexistence between humans and primates,” added co-author and field researcher Randall C. Kyes, PhD.

Photo Credit: Randall C. Kyes, PhD

Ever wonder how your brain knows what a certain object is, even if the object is mostly hidden? Researchers at the Washington National Primate Research Center (WaNPRC) at the University of Washington (UW) may have discovered an explanation for this phenomenon.

Researchers studied brain signals and tracked eye movements in rhesus monkeys while the animals played a computer game in which they attempted to identify half-hidden, two-dimensional objects and specific shapes.

“Basically, when the task is simple, (the) visual cortex works just fine, but when the task becomes difficult, there needs to be communication between a higher brain region involved in memory and learning,” Anitha Pasupathy, PhD, Associate Professor at the UW School of Medicine Department of Biological Structure, said about the results of the study.

These findings make the researchers wonder if impaired communication between the brain’s thinking and sensory parts might lead to certain difficulties, like confusion in cluttered surroundings, for people who have autism or Alzheimer’s.   

“This, for us, is a very exciting demonstration because it breaks open a whole lot of questions we can ask about how different brain areas interact to solve this important problem of visual recognition,” noted Pasupathy.

The scientists said the next step in their research is to determine if more brain areas are involved in recognizing objects with more complex images.

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Photo credit: Kathy West for the California National Primate Research Center

Since the Zika virus epidemic of 2015, there has been a surge in the number of infants in the Americas born with small heads due to brain damage that occurred when their mothers were infected during pregnancy, a condition called microcephaly.

Scientists previously thought this condition was the primary indicator of brain damage due to Zika infection, but researchers at Washington National Primate Research Center (WaNPRC) have discovered damage may still be present when head size is normal.

“Current criteria using head size to diagnose Zika-related brain issues fail to capture more subtle brain damage that can lead to significant learning problems and mental health disorders later in life,” said Kristina Adams Waldorf, MD, FACOG, a professor of obstetrics and gynecology at the UW School of Medicine who specializes in maternal and fetal infections. “We are diagnosing only the tip of the iceberg.”

In addition to Adams Waldorf, the lead researchers were Michael Gale Jr., PhD, a professor of immunology at the UW School of Medicine and an expert on how the body responds to viruses, and Lakshmi Rajagopal, PhD, an associate professor of pediatrics at the University of Washington School of Medicine and expert on newborn infectious diseases at Seattle Children’s Research Institute and UW School of Medicine.

According to the researchers, even children with a normal head size at birth may be diagnosed with serious eye injuries or late-onset microcephaly when the head fails to grow normally. Damage may also occur in children infected during early childhood and adolescence. In addition, it’s possible undetected Zika brain damage may later lead to learning disorders, psychiatric illnesses and dementia.

In the study, researchers looked for subtle changes in the brains of five fetal macaques whose mothers had been infected with the Zika virus in pregnancy. In all but one case, the researchers found no obvious fetal abnormalities with weekly ultrasounds, a medical imaging technique that is commonly used during pregnancy to assess the health of developing fetuses.

The brains of the infected fetuses, however, did grow more slowly than normal, but they remained large enough so their smaller size did not meet the criteria for Zika virus-associated microcephaly the U.S. Centers for Disease Control and Prevention uses. Under these criteria, most children (between 91 percent to 96 percent) born in the United States whose mothers were infected with Zika during the pregnancy are also not considered microcephalic. As a result, those children might not be checked regularly for Zika-related brain injury.

Magnetic resonance imaging (MRI) scans of the fetal brains, however, were abnormal in 4 of 5 of the animals. Certain areas of the brain were not growing as quickly as others. Brain regions particularly affected were areas that generate new brain cells, including the subventricular zone in the wall of the lateral ventricle, which contains the largest number of neural stem cells in the brain. Another injured part of the fetal brain was the subgranular zone of the dentate gyrus in the hippocampus, where neural stem cells play a key role in memory and learning and continue to contribute to brain health through at least adolescence.

“The study clearly shows that cells within these brain regions are highly susceptible to Zika virus infection. The findings suggest that neural stem cells within these sites, and at specific stages of development, are unable to suppress virus replication,” noted Gale.

Gale added these findings further emphasize the urgency for an effective vaccine to prevent Zika virus infections. The researchers also concluded Zika-exposed fetuses should continue to be checked for symptoms of the disease throughout their developmental years.

“All children exposed to Zika virus in utero should be followed long-term for problems with learning and development, regardless of head size at birth,” Adams Waldorf said.

For most of us, getting a flu shot ranks among the least exciting annual events. But researchers at the Washington National Primate Research Center (WaNPRC) at the University of Washington (UW) are hoping to make this yearly obligation a thing of the past.

A team led by Deborah Fuller, a professor in the Department of Microbiology at the UW School of Medicine, is testing the effectiveness of a universal vaccine that protects from every strain of influenza virus, even when the viruses transform genetically from year to year. Working with cynomolgus macaques, the researchers have seen promise using a DNA vaccine that instructs skin cells to produce antigens, while inducing antibodies and T cell responses to fight flu infection.

The vaccine was created using genetic components of influenza virus that remain constant. This feature allows the vaccine to get around the genetic drift, or changes, that occur in influenza strains from year to year.

“With the immunized groups, we found that using this conserved component of the virus gave them 100 percent protection against a previous circulating influenza virus that didn’t match the vaccine,” Fuller said. “This was very exciting for us.”

The DNA vaccine is administered through the epidermis with a “gene gun” device, which injects the vaccine directly into the skin cells. The cells then produce the flu vaccine and prompt the body to actively fight infection. This is an improvement over current on-the-market vaccines, which simply repel the virus.

This approach also takes less time to produce—about three months—than the nine months required to produce the current U.S.-approved vaccine.

“We’ve been working essentially with the same vaccine (techniques) over the last 40 years,” Fuller noted. “It’s been a shake-and-bake vaccine: You produce the virus, you kill the virus, you inject it. Now it’s time for vaccines to go through an overhaul, and this includes the influenza vaccine.”

Fuller said that this kind of universal vaccine could eliminate the need for yearly flu vaccinations and be kept on-hand for rapid deployment in response to a deadly pandemic strain of the virus.

She added that DNA-based vaccines may also prove effective for different viruses, like Zika, and for other possible serious outbreaks.

Understanding the genetic code is one thing. Altering it is something different altogether. Researchers at the Washington National Primate Research Center (WaNPRC) have discovered a technique for inserting a specific gene into the brain’s membrane, which could modify how the brain works, alter behavior, and potentially correct neurological disorders.

Researchers think that this approach, which involves genetically altering a select number of cells, might lead to treatments for neurological conditions such as epilepsy. “The brain is made up of a mix of many cell types performing different functions. One of the big challenges for neuroscience is finding ways to study the function of specific cell types selectively without affecting the function of other cell types nearby,” said lead researcher and associate professor of physiology and biophysics Gregory Horwitz. “Our study shows it is possible to selectively target a specific cell type in an adult brain using this technique and affect behavior nearly instantly.”

The research team inserted a gene into cells in the cerebellum, the parts of the brain controlling motor movements. Those cells, Purkinje cells, are some of the largest in the brain and connect with hundreds of other cellular structures.

The inserted gene, channelrhodopsin-2, creates a light-sensitive protein that inserts itself into the brain cell’s membrane. When exposed to light, the protein allows ions – tiny charged particles – to pass through the membrane.

By attaching the gene to a modified virus and painlessly injecting it into a small area of the cerebellum of rhesus macaque monkeys, the channelrhodopsin-2 was taken up exclusively by the targeted Purkinje cells. The researchers then showed that when they exposed the treated cells to light, they could affect motor control.

“This ‘transgenic’ approach has proved invaluable in the study of the brain,” Horwitz said. “But if we are someday going to use it to treat disease, we need to find a way to introduce the gene later in life, when most neurological disorders appear.” With this discovery, the researchers are one step closer to understanding the elegant system that is the brain.

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Photo credit: Kathy West for the California National Primate Research Center

Are vaccines tied to an increased risk of autism? That’s the question researchers at the Washington National Primate Research Center (WaNPRC) are working to answer. While scientific research continues, the results of a recent study shows no obvious connection between following a vaccination schedule and brain defects.

The study focused on vaccines containing thimerosal, a chemical designed to protect the vaccine from bacterial contamination. This mercury-based compound, after decades of use, has largely been phased out at the recommendation of the Food and Drug Administration because of fears about an overexposure to mercury. However, flu and meningitis vaccines continue to use thimerosal.

“It is of great importance to determine whether childhood vaccines that contain this preservative play a significant role in altering brain development, such as autism,” said lead investigator Dr. Laura Hewitson of The Johnson Center for Child Health and Development and affiliate investigator with the WaNPRC.

Using a nonhuman primate model, the study showed no negative side effects such as rocking, self-clasping, or other repetitive behaviors after exposure to thimerosal-containing vaccines. In addition, research didn’t identify any noticeable neurochemical distinctions between vaccinated and unvaccinated test models.

This discovery is good news for advocates of childhood vaccinations, and by connection, for millions of kids  who receive vaccines each year. However, until there is a definite answer, the National Primate Research Centers will continue this research.

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Photo credit: Kathy West for the California National Primate Research Center