September 28, 2020

The seven National Primate Research Centers (NPRCs) are participating in SciFest All Access 2020. This is the virtual answer to the postponed USA Science & Engineering Festival, which is recognized as the nation’s top science and engineering festival for K-12 students, college students, educators and families. Happening now through Oct. 3, registered participants can visit the NPRCs in the “Exhibit Portal, Health & Medicine Zone II.”

The NPRC booth includes links to NPRC.org, our collective website, as well as individual web pages for the seven centers. All pages are filled with educational resources and links to help you learn more about our research, the scientific advancements we’re making and the care we provide our research animals. Direct access links to these seven pages are provided below.

NPRC representatives will be “on site” at SciFest All Access answering questions registered participants submit via the “Ask a Question” link in the booth. We’re also answering questions participants email us at nprcoutreach@gmail.com.

You can learn even more about the NPRCs’ research to improve human and animal health by visiting NPRC.org and following us on Twitter at @NPRCnews.

We look forward to joining thousands of students, educators and families at this year’s SciFest All Access!

SciFest All Access NPRC Web Pages

California NPRC

Oregon NPRC

Southwest NPRC

Tulane NPRC

Washington NPRC

Wisconsin NPRC

Yerkes NPRC

July 30, 2020

Could HIV vaccines be reducing their own effectiveness by stimulating too much help? According to scientists at Yerkes National Primate Research Center (YNPRC), this could be the case.

In a recent paper that considered information from four studies on macaques immunized against SIV (HIV’s relative) or the hybrid SHIV virus, the researchers concluded a certain type of immune system cell known for helping may actually represent a weak spot in the body’s defenses.

HIV targets and replicates inside helper T cells, which aid in the body’s antiviral immune response. The problem comes when vaccination generates too many of a particular type of helper immune cell, Th1 cells.

We can think of Th1 cells as the well-intentioned first responders to a zombie attack. These cells travel to mucosal tissues, such as the rectum, cervix and vagina, where HIV/SIV first enters the body in the majority of infections. Th1 cells combat the virus initially, but then they get taken over.

What’s needed instead are Tfh cells, which remain in the lymph nodes and aid the immune system in creating antibodies. 

“We’re not saying Th1 cells are bad,” noted Rama Rao Amara, PhD, YNPRC and Emory Vaccine Center researcher, and co-director of Emory’s Consortium for Innovative AIDS Research in Nonhuman Primates. “But if you have too many, they take away from effective vaccine protection.”

“It’s a matter of stimulating just the right amount of immune help for a strong immune response, but not so much that it increases susceptibility to the virus,” added Eric Hunter, PhD, co-author and co-director with Amara of the AIDS research consortium, and an Emory Vaccine Center researcher. 

This could possibly be achieved using adjuvants, which are vaccine components that enhance the immune response. Amara noted the need for the effects of adjuvants to be explored in future research, and he further stated scientists studying candidate HIV vaccines in humans should examine whether these vaccines create too many Th1 target cells. This information could help immunologists design vaccines that provide more reliable protection against HIV.

Researchers across the NPRC network continue to explore new treatments for HIV/AIDS every day. You can keep up with the latest breakthroughs here.

July 21, 2020

While much progress has been made during the last few years in combating and preventing the deadly Zika virus, researchers are still working toward a greater understanding of how the disease affects the development of the brain in newborns.

Recently, scientists at the Yerkes National Primate Research Center (YNPRC) made a breakthrough by showing Zika virus infection, soon after birth, leads to long-term brain and behavior problems. The study is one of the first to shed light on potential long-term effects of Zika infection during infancy.

“Researchers have shown the devastating damage Zika virus causes to a fetus, but we had questions about what happens to the developing brain of a young child who gets infected by Zika,” says lead researcher Ann Chahroudi, MD, PhD, an affiliate scientist in the Division of Microbiology and Immunology at Yerkes, director of the Center for Childhood Infections and Vaccines (CCIV), Children’s Healthcare of Atlanta (CHOA) and Emory University, and an associate professor of pediatrics in the Division of Pediatric Infectious Diseases at Emory University School of Medicine.

The study followed four infant rhesus monkeys for one year after Zika virus infection at one month of age. Studying a rhesus monkey until the age of one translates to the equivalent of four to five years in human age.

Researchers found postnatal Zika virus infections led to significant changes in behavior—including reduced social interactions and increased emotional reactions—and some impairments in memory and gross motor abilities. 

“These changes corresponded with structural and functional brain changes we found on MRI scans,” says researcher Jessica Raper, PhD, research assistant professor at Yerkes. “This is especially important because it allows us to confirm the neurologic findings lead to ongoing and noticeable changes in behavior,” she continues. 

The researchers also noted this finding will give healthcare providers a greater understanding of the possible complications of Zika infection following pregnancy and birth.

“Our results shed light on potential outcomes of human infants infected with Zika virus after birth and provide a platform to test treatments to alleviate long-term neurologic consequences of Zika infection,” says Chahroudi. “Our research team encourages future studies to understand the impact of early postnatal Zika infection during later stages of life, from adolescence to adulthood.”

More than 85 countries and territories have reported evidence of mosquito-acquired Zika virus infection, for which there is no cure or treatment medications. Zika virus and the mosquitoes that transmit it have not been eliminated, and so transmission remains a risk.

Research related to the prevention and treatment of Zika at the NPRCs is ongoing. You can learn more about our studies and findings here. 

The study in this article was highlighted by the editors of Nature Communications on a dedicated webpage for brain and behavioral research.

 

June 24, 2020

While antiviral medications limit the impact of the disease on daily life, human immunodeficiency virus (HIV) continues to infect 1.7 million people annually and cause some 770,000 deaths each year, which makes research on the virus a high priority.

Recently, a team that includes researchers from the Yerkes National Primate Research Center (YNPRC) at Emory University showed a new HIV vaccine is better at preventing infection and also lasts longer.

According to the researchers, the new vaccine’s improved protection lies in the combination of two types of immune responses: “neutralizing” antibodies and cellular immunity, a process involving the activation of T cells.

”Most efforts to develop an HIV vaccine focus on activating the immune system to make antibodies that can inactivate the virus, so-called neutralizing antibodies,” said Eric Hunter, PhD, professor of pathology and laboratory medicine at Emory, and a researcher at the Emory Vaccine Center (EVC) and YNPRC. “We designed our vaccine to also generate a strong cellular immune response that homed in on mucosal tissues so the two arms of the immune response could collaborate to give better protection,” he continues.

In the study, the researchers inoculated three groups of 15 monkeys during a 40-week period.

The first group received Env, a protein on the virus’ outer surface known for stimulating antibody production, plus an adjuvant, a chemical combination often used in vaccines to enhance immune response.

The second group received the same, plus additional injections of three different attenuated (weakened) viruses modified to contain the gene for an HIV viral protein, Gag, which is known to stimulate cellular immunity.

A third, the control group, received injections containing only the adjuvant.

Following the 40-week regimen, all animals rested for 40 weeks, and then the researchers gave them booster shots of just the Env inoculation. After resting four more weeks, the researchers gave the animals 10 weekly exposures to SHIV, the simian version of HIV.

The results revealed animals in the two experimental groups experienced significant initial protection from viral infection if their immune system had a strong showing of neutralizing antibodies. Even more notable, say the researchers, was several of the Env-plus-Gag animals—but none of the Env animals—remained uninfected even though they lacked robust levels of neutralizing antibodies.

This outcome is exceptional because the potency of neutralizing antibodies has previously been thought to be crucial to a vaccine’s effectiveness. What’s more, when the researchers rechallenged the protected animals six months after the first challenges, the Env-plus-Gag animals but not the Env animals maintained protection, which shows the protection is durable.

“These results open exciting opportunities for HIV vaccines,” said Rama Amara, PhD, a Yerkes and EVC researcher and professor of microbiology and immunology at Emory. We now know it’s possible to achieve durable protection against HIV with a low response of neutralizing antibodies as long as the vaccine induces T cells.”

The team will use these results to refine the way it approaches vaccine development, noting a similar approach could possibly be feasible for other pathogens, including influenza, tuberculosis, malaria and COVID-19.

As the search for a cure continues, scientists across the NPRC network are working to discover new ways of treating and preventing HIV. Learn more about similar studies here.

 

April 2, 2020

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

News articles by 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.

 

March 21, 2020

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/covid/signs-symptoms/?CDC_AAref_Val=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/covid/?CDC_AAref_Val=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.

December 19, 2019

Cells that harbor HIV, even while a person is on antiretroviral drugs, are referred to as the “reservoir”. Some of these cells might be able to self-renew/proliferate, thus continually replenishing the virus reservoir. The elusive task of “drying up” this reservoir is key in uncovering a cure.

Researchers at Yerkes National Primate Research Center (YNPRC) recently tested the possibility to block the reservoir self-renewal, working with macaques infected with SIV (Simian immunodeficiency virus) and targeting the Wnt/beta-catenin pathway during antiretroviral therapy. 

Wnt is a common signaling pathway, and beta-catenin is a central protein in that pathway. Beta-catenin regulates the balance between self-renewal and differentiation (changing to another cell type, more mature and shorter-lived) of memory T cells.

The team used PRI-724, a molecule that blocks interaction between beta-catenin and another protein beta-catenin needs to turn on genes. The researchers noted decreased proliferation of long-lived memory T cells and signs of more differentiation into shorter-lived cells that are more prone to die. However, short-term treatment with PRI-724 alone didn’t significantly reduce the size of the overall viral reservoir.

The scientists noted, though, it may be possible PRI-724 or a similar drug could be combined with other approaches for a longer time to make a greater impact.

They also pointed out this technique differs from the “shock and kill” approach that activates dormant infected T cells to trigger an immune system response. NPRC scientists are testing this approach in separate, ongoing studies.

November 25, 2019

People who suffer from post-traumatic stress disorder (PTSD) and other stress- and anxiety-related conditions experience debilitating bouts of fear when they encounter certain environmental cues. In some cases, these bouts of fear come about when cues that merely resemble those that were directly associated with a traumatic or stressful episode are encountered. As a result, individuals find themselves becoming paralyzed with fear when they encounter harmless cues in their environment.

This is called fear generalization, and it can significantly hamper one’s quality of life. The major question for researchers is: What happens in the brain to cause this generalized fear? 

Previous research has focused on the amygdala, prefrontal cortex and hippocampus, all brain regions that monitor and detect threatening stimuli. However, a new study from the Yerkes National Primate Research Center (YNPRC) has demonstrated the zona incerta (ZI), a brain region previously thought insignificant, may play an important role.

Scientists at the YNPRC mapped and manipulated brain activity in the ZI of mice that demonstrated fear toward neutral stimuli of which they should not have been fearful.

Review of the neural activity in the mice’s brains revealed the ZI was less active in mice that showed fear generalization, and stimulating specific cells in the ZI dramatically reduced fear generalization. This suggests the ZI might serve to halt exaggerated fear responses.

These findings could hold therapeutic value for suppressing debilitating fear generalization and helping thousands of people with stress- and anxiety-related disorders live calmer, happier lives.

July 15, 2019

Sometimes it really does take two. 

Scientists at Yerkes National Primate Research Center (YNPRC) at Emory University in Atlanta have discovered that a form of antibiotic resistance called “heteroresistance” is more widespread than previously thought, but attacking bacteria with combinations of antibiotics may hold the key to defeating them.

“We can think of heteroresistance as bacteria that are ‘half resistant’,” said David Weiss, PhD, director of the Emory Antibiotic Resistance Center, an associate professor of medicine (infectious diseases) and a researcher at the YNPRC. “This is because only some of the cells in the population exhibit resistance. When you take the antibiotic away, the resistant cells go back to being just a small part of the group. That’s why they’re hard to see in the tests that hospitals usually use.”

In exploring the heteroresistance phenomenon, Weiss and his colleagues examined 104 bacterial isolates, tracking multi-drug resistant superbugs. They found more than 85 percent were heteroresistant to at least two antibiotics. Weiss and his team then made their major discovery: Combining two antibiotics to which each superbug was heteroresistant proved effective at killing them. 

This occurred, they found, because the heteroresistant sub-populations were independent. If scientists grew the bacteria in the presence of one antibiotic, or knocked out resistance to that antibiotic genetically, this didn’t affect heteroresistance to any other antibiotics. 

Previously, microbiologists have thought some combinations of antibiotics might work together synergistically — one antibiotic working to weaken one part of the bacteria, while the other hits a different spot. But Weiss indicated the reasons combinations work might largely be explained by heteroresistance to multiple drugs. 

Using this knowledge, scientists are encouraged they will be able to help healthcare professionals more effectively use antibiotics to defeat bacteria that have developed resistance. 

“We’re saying: even if a strain of bacteria is classified as resistant to some antibiotics, don’t toss those drugs in the trash, they may still have some utility,” Weiss explained. “The ones targeting heteroresistance just have to be used in combination with others to do so.”

June 17, 2019

What if certain parts of the brain could be turned off to treat neurological disorders like Parkinson’s disease? Though it seems far-fetched now, such a solution could soon become reality.

During the last 10 years, the field of neuroscience research has been revolutionized by new genetic techniques, allowing neuroscientists to express artificial proteins in neurons that can then be modified to study diseases and disorders. One of the most commonly used genetic-based approaches is called chemogenetics.

Chemogenetic techniques use artificial receptor proteins that only become active in the presence of a specific drug. This means only the neurons containing the artificial receptor will change their activity in response to the drug, while other neurons remain unaffected. We can think of it as a chemical switch that turns specific neurons on or off.

While chemogenetics methods have been extensively used in basic research, they have yet to be translated to clinical treatment. However, researchers have recently developed new chemogenetic tools that have the potential to be used in clinical applications. The team, led by Scott Sternson (Howard Hughes Medical Institute’s Janelia Research Campus), included Yerkes National Primate Research Center researchers Adriana Galvan, PhD, and Xing Hu, MD.

In this new chemogenetic system, the researchers activated the artificial receptors by using drugs specifically designed for the receptors, as well as varenicline (Chantix™), an antismoking drug. The receptors and drugs were optimized during in vitro experiments and then successfully used to control the activity of neurons in rodents.

The Yerkes researchers then contributed an important step toward potential clinical application of the tools by duplicating the effects in a nonhuman primate’s brain. When the primate received a low dose of varenicline, the neurons containing the artificial receptors were silenced — all with no observable side effects. The results provide a critical proof of concept that chemogenetic methods can be effectively used in nonhuman primate studies.

Yerkes researchers are now expanding the chemogenetic experiments with the aim of using them in a nonhuman primate model of Parkinson’s disease, which is characterized by some movement-related brain regions being abnormally active. Chemogenetic manipulation could potentially silence or at least modulate the activity of these brain areas and help scientists develop a novel Parkinson’s therapy.

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