April 27, 2021

Did you know the rhesus macaque is the most widely studied nonhuman primate in biomedical research? The U.S. research colonies of rhesus macaques were founded primarily with animals imported from India decades ago and with the addition of Chinese-origin rhesus macaques over time. A deep understanding of their evolution and genetics is key to recognizing the origins of human traits and identifying disease genes of value to improving human health.

Rhesus macaques at the seven National Primate Research Centers (NPRCs) are key in the discovery and development of new and robust models of human disease and in evaluating the effect of genetic variation on experimental treatments prior to human clinical trials.  

In a recent publication in Science that detailed researchers’ use of advanced sequencing technology and analysis of more than 850 macaques across the seven NPRCs, researchers present a complete reference genome for the rhesus macaque. “In particular, we can now finally tackle some of the more complex regions of the genome and begin to understand how new genes evolve including the processes that have shaped them,” says University of Washington genome sciences professor and senior author in the paper, Evan Eichler, PhD.

In addition, the study identified animals that naturally carry potentially damaging genetic mutations, allowing researchers to better understand genetic variation and susceptibility to diseases of relevance to humans. So far, the findings reveal thousands of naturally occurring genetic variants (mutations), including those in genes linked to Autism Spectrum Disorder and other neurodevelopmental disorders in humans, such as SHANK3.

Jeffrey Rogers, PhD, associate professor at the Human Genome Sequencing Center and Department of Molecular and Human Genetics at Baylor College of Medicine and co-author of the paper explains, “Rhesus macaques are important for studies of conditions ranging from infectious disease (including COVID-19) to neuroscience, cancer and reproductive biology. A high-quality reference genome can aid researchers who are looking to understand the causes of various illnesses or aiming to develop treatments.”

The study is a great example of a broad collaboration across the NPRCs and other research centers in the U.S. that will continue to make a difference in human health. By identifying rhesus macaques that carry naturally occurring mutations, NPRC and other researchers are now able to examine biobehavioral traits associated with mutations. The researchers can also follow the monkeys’ offspring, and, in some cases, actually create new breeding groups to generate animals with specific genetic mutations and phenotypes. 

“This new information will lay the foundation for us to create naturally occurring models of human genetic diseases,” says Paul Johnson, MD, director of the Yerkes NPRC. “The development of these new models could have a profound impact on our ability to translate research in animal models into treatments and cures in people,” he continues.

To learn more about NPRC advances in genetics and genomics, explore additional research here

March 3, 2021

Scientific discovery is an ongoing process that takes time, observation, data collection and analysis, patience and more. At the NPRCs, our recent COVID-19 research is an example of the ongoing basic science process — how current research builds on previous discoveries and how discoveries help improve human health. This article from the National Institutes of Health (NIH) explains why basic science, such as the NPRCs conduct, is important and how taking time, as long as it takes, is a necessary part of scientific discovery.

Discoveries in Basic Science: A Perfectly Imperfect Process

Have you ever wondered why science takes so long? Maybe you haven’t thought about it much. But waiting around to hear more about COVID-19 may have you frustrated with the process.

Science can be slow and unpredictable. Each research advance builds on past discoveries, often in unexpected ways. It can take many years to build up enough basic knowledge to apply what scientists learn to improve human health.

“You really can’t understand how a disease occurs if you don’t understand how the basic biological processes work in the first place,” says Dr. Jon Lorsch, director of NIH’s National Institute of General Medical Sciences. “And of course, if you don’t understand how the underlying processes work, you don’t have any hope of actually fixing them and curing those diseases.”

Basic research asks fundamental questions about how life works. Scientists study cells, genes, proteins, and other building blocks of life. What they find can lead to better ways to predict, prevent, diagnose, and treat disease.

How Basic Research Works

When scientists are interested in a topic, they first read previous studies to find out what’s known. This lets them figure out what questions still need to be asked.

Using what they learn, scientists design new experiments to answer important unresolved questions. They collect and analyze data, and evaluate what the findings might mean.

The type of experiment depends on the question and the field of science. A lot of what we know about basic biology so far has come from studying organisms other than people.

“If one wants to delve into the intricate details of how cells work or how the molecules inside the cells work together to make processes happen, it can be very difficult to study them in humans,” Lorsch explains. “But you can study them in a less complicated life form.”

These are called research organisms. The basic biology of these organisms can be similar to ours, and much is already known about their genetic makeup. They can include yeast, fruit flies, worms, zebrafish, and mice.

Computers can also help answer basic science questions. “You can use computers to look for patterns and to try to understand how the different data you’ve collected can fit together,” Lorsch says.

But computer models have limits. They often rely on what’s already known about a process or disease. So it’s important that the models include the most up-to-date information. Scientists usually have more confidence in predictions when different computer models come up with similar answers.

This is true for other types of studies, too. One study usually only uncovers a piece of a much larger puzzle. It takes a lot of data from many different scientists to start piecing the puzzle together.

Building Together

Science is a collective effort. Researchers often work together and communicate with each other regularly. They chat with other scientists about their work, both in their lab and beyond. They present their findings at national and international conferences. Networking with their peers lets them get feedback from other experts while doing their research.

Once they’ve collected enough evidence to support their idea, researchers go through a more formal peer-review process. They write a paper summarizing their study and try to get it published in a scientific journal. After they submit their study to a journal, editors review it and decide whether to send it to other scientists for peer review.

“Peer review keeps us all informed of each other’s work, makes sure we’re staying on the cutting-edge with our techniques, and maintains a level of integrity and honesty in science,” says Dr. Windy Boyd, a senior science editor who oversees the peer-review process at NIH’s scientific journal of environmental health research and news.

Different experts evaluate the quality of the research. They look at the methods and how the results were gathered.

“Peer reviewers can all be looking at slightly different parts of the work,” Boyd explains. “One reviewer might be an expert in one specific method, where another reviewer might be more of an expert in the type of study design, and someone else might be more focused on the disease itself.”

Peer reviewers may see problems with the experiments or think different experiments are needed. They might offer new ways to interpret the data. They can also reject the paper because of poor quality, a lack of new information, or other reasons. But if the research passes this peer review process, the study is published.

Just because a study is published doesn’t mean its interpretation of the data is “right.” Other studies may support a different hypothesis.

Scientists work to develop different explanations, or models, for the various findings. They usually favor the model that can explain the most data that’s available.

“At some point, the weight of the evidence from different research groups points strongly to an answer being the most likely,” Lorsch explains. “You should be able to use that model to make predictions that are testable, which further strengthens the likelihood that that answer is the correct one.”

An Ever-Changing Process

Science is always a work in progress. It takes many studies to figure out the “most accurate” model—which doesn’t mean the “right” model.

It’s a self-correcting process. Sometimes experiments can give different results when they’re repeated. Other times, when the results are combined with later studies, the current model no longer can explain all the data and needs to be updated.

“Science is constantly evolving; new tools are being discovered,” Boyd says. “So our understanding can also change over time as we use these different tools.”

Science looks at a question from many different angles with many different techniques. Stories you may see or read about a new study may not explain how it fits into the bigger picture.

“It can seem like, at times, studies contradict each other,” Boyd explains. “But the studies could have different designs and often ask different questions.”

The details of how studies are different aren’t always explained in stories in the media. Only over time does enough evidence accumulate to point toward an explanation of all the different findings on a topic.

“The storybook version of science is that the scientist is doing something, and there’s this eureka moment where everything is revealed,” Lorsch says. “But that’s really not how it happens. Everything is done one increment at a time.”

 

December 18, 2020

Researchers at Yerkes National Primate Research Center (YNPRC) have discovered a way to use cancer immunotherapy treatments to reliably shrink the size of the viral “reservoir” in simian immunodeficiency virus (SIV)-infected nonhuman primates treated with antiviral drugs.

In humans, antiviral drugs can suppress human immunodeficiency virus (HIV) to the point of being undetectable in blood, but the virus embeds itself in the DNA of specific immune cells (T cells). Each reservoir consists of T cells that continue to harbor the virus even during antiviral drug treatment.

According to the researchers, chronic viral infection and cancer produce similar states of “exhaustion.” T cells that could fight virus or cancer are present but unable to respond. In long-term HIV or SIV infection, T cells harboring the virus display molecules on the cell surface that make them targets for checkpoint inhibitors (cancer immunotherapy drugs designed to counteract the exhausted state).

In this study, researchers combined two cancer immunotherapy treatments to block the surface molecules CTLA-4 and PD-1 in nonhuman primates. In subjects that received both CTLA-4- and PD-1-blocking agents, researchers noted a stronger activation of T cells compared to only a PD-1 blockade.

“We observed that combining CTLA-4 and PD-1 blockade was effective in reactivating the (SIV) virus from latency and making it visible to the immune system,” said Mirko Paiardini, PhD, an associate professor of pathology and laboratory medicine at Emory University School of Medicine and a researcher at YNPRC.

In previous studies, shrinkage of the viral reservoir has been limited and inconsistent when researchers use single checkpoint inhibitors or other immune-stimulating agents. During this study, however, combination-treated animals showed a consistently measurable and significant reduction in the size of the viral reservoir.

Despite these findings, the combination treatment does not prevent or delay viral rebound once antiviral drugs are stopped. Paiardini suggested the approach may have greater potential if combined with other strategies, for example a therapeutic vaccine, or it could be deployed in a target-rich environment, for example during ART interruption when the immune system is engaged in intercepting and fighting the rebounding virus. Other HIV researchers have started to test those tactics, he indicated.

It is also noteworthy the equivalent combination of CTLA-4 and PD-1 blockade in humans has been tested in the context of cancer treatment, and while the two drug types can be more effective together, patients sometimes experience adverse side effects like severe inflammation, kidney damage or liver damage. Fortunately, the combination-treated animals in this study did not experience comparable events.

Finding a complete HIV cure is still critically important because problematic issues, like social stigma and the long-term toxicity and cost of antiretroviral drugs, remain. 

To learn more about how NPRC scientists are working toward effective treatments—and ultimately a cure—visit this link.

December 15, 2020

Research with animals is crucial to improving human and animal health. Animals in research provide unique insights not available with other scientific models, and they help scientists determine safety and effectiveness of preventions, treatments and cures. During the COVID-19 pandemic, animals in research have been especially important in accelerating the development COVID-19 vaccines as well as better diagnostics and additional treatment options.

At the NPRCs, we’re helping fill a critical role in halting COVID-19 by leading NIH-funded studies at our centers. We’re also participating in the public-private partnership ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines) to develop treatments and vaccines by sharing our knowledge, resources and animals, including conducting preclinical studies with NPRC monkeys for some of the leading industry vaccine candidates.

Scientific collaboration is especially important during a pandemic when time is of the essence and, in this case, animal resources are limited. At the onset of the pandemic, monkey importation was halted, putting increasing demands on the NPRC animal colonies, which were already limited in quantity and availability. The NPRCs account for only 1 in every 5 nonhuman primates (NHPs) used in U.S.-based research, so the limited supply at a time of high demand impacts NPRC COVID-related studies as well as pre-pandemic studies under way at the NPRCs and those in planning stages.

The NPRCs remain dedicated to our other areas of study, including research into HIV/AIDS and other infectious diseases, the neurosciences, cardiovascular and respiratory health, genetics and transplant medicine. 

We are also committed to meeting the future needs of animals for NIH-funded research. This is why the NPRCs support establishing a strategic reserve of NHPs to be used in times of national health crises. We are already growing our on-site breeding colonies when time, space and funding permit, strategically assigning animals to research protocols, harmonizing across centers for efficient use of animals and increasing rigor and reproducibility to facilitate collaboration and consistency across research labs. These strategic steps now further position the NPRCs for the translation of our research advancements from cell and animal models to humans, and are indicative of our commitment to help people across generations and the world live longer, healthier lives. 

To learn more about the NPRCs’ ongoing efforts to combat COVID-19, visit this page.

Editor’s Note, 2/22/21: The New York Times covered the research monkey shortage in today’s issue. Read the story here.

November 30, 2020

Could a promising discovery about viral latency help scientists effectively combat human immunodeficiency virus (HIV)?

The primary obstacle to a cure for HIV infection is the reservoir, or immune cells that harbor the inactive virus when someone is being treated with antiretroviral drugs. One of the leading research strategies for eliminating HIV from the body is “shock and kill,” which involves activating a dormant virus from within these immune cells where it hides, then eliminating it. A key challenge, however, has been finding a safe way to “wake up” the virus from its latent state.

In two complementary studies—one from the Yerkes National Primate Research Center (YNPRC) of Emory University and another from the University of North Carolina at Chapel Hill—researchers report they have come closer to that goal.

The studies relied on two animal models of HIV infection. Each took a different approach, but both yielded promising results, bringing the virus out of its hiding places even in the presence of antiretroviral drugs that stopped it from replicating for months.

“If our goal is to cure HIV/AIDS, then we have to disrupt viral latency,” said Guido Silvestri, MD, chief of microbiology and immunology at the YNPRC. “What we’re doing now is a new combination approach that provides unprecedented levels of virus reactivation.”

Both approaches were tested at the YNPRC in monkeys infected with SIV, a close relative of HIV, and treated with antiretroviral drugs. At UNC, tests were also conducted in mice transplanted with human immune cells. The results represented the first occurrence of a successful systemic HIV induction in humans or an animal model with human cells that was then replicated in a completely different species infected with a different virus.

In one study, 12 monkeys were treated with the drug AZD5582, and just one experienced a temporary fever and loss of appetite—a promising sign. In the other study, researchers stimulated the cells that are the main viral hosts (CD4+ T cells) while also depleting another kind of immune cell (CD8+ T cells), which normally keeps the virus in check. The scientists indicated both the stimulation and depletion components were necessary to see SIV re-emerge.

Neither intervention mentioned above, however, reduced the size of the viral reservoir. Once the animals were taken off antiretroviral drugs, viral levels rebounded. The scientists indicated that in future studies, the initial viral reactivation needs to be combined with other modes of treatment, such as antibodies directed against the virus itself.

Want to learn more about how researchers are working toward a cure for HIV? Take a look at some other related studies from the NPRCs, including this one about reducing the viral reservoir.

November 24, 2020

Talking about animals in research may not be part of everyday conversations – unless you work in research, are learning more about it or want to stop it. But if everyone knew how critical animals have been in 2020 to fast-track a safe and effective COVID-19 (coronavirus) vaccine, would that change?

Earlier this year, the National Institutes of Health (NIH) called upon the National Primate Research Centers (NPRCs) – as NIH has for HIV/AIDS, Ebola, Zika and other infectious disease threats – to identify animal species for studying the SARS-CoV-2 virus and developing safe and effective vaccines to block it.

The NPRCs went to work and within a few months had discovered how valuable nonhuman primate models (NHPs), especially macaques, are for studying SARS-CoV-2. The NPRCs found the virus infects rhesus, pigtail and cynomolgus macaques, so these animals were included in research programs that resulted in several vaccine candidates in the pipeline by summer’s end. In addition, other key models for SARS-CoV-2, such as mice and hamsters, contributed to the broadening knowledge of how best to tackle the disease in humans. This rapid pace of discovery was possible due to the NPRC researchers applying their expertise fighting other viruses, especially HIV/AIDS.

As with those other viruses, the NPRC researchers closely studied SARS-CoV-2 transmission routes and pathogenesis – this time focusing on the respiratory virus’ activity in the lungs and its impact on cells, tissues and organs. The researchers also conducted detailed genetic studies on the virus to help pharmaceutical researchers use pieces of the virus’ genetic code to fashion vaccine candidates and test them for safety and effectiveness in macaques.

Translating the biomedical research findings into the human population requires going from up to a few dozen monkeys in research to thousands of human volunteers in clinical trials; for COVID-19, more than 200,000 volunteers have enrolled in four promising clinical trials. As announced in November 2020, the Moderna and Pfizer mRNA vaccines tested on rhesus macaques were more than 90 percent effective in preventing COVID-19 in widespread (Phase 3) human clinical trials and are now on track for emergency FDA approval.

Research with animals connects these vaccines with other SARS-CoV-2 scientific advancements just as it has made connections among NPRC HIV/AIDS studies, the results from which facilitated the rapid pace to COVID-19 discoveries. Improving human and animal health – that’s what NPRC research with animals does, and that’s worth talking about any day.

Learn more about research with animals scientific advancements here.

October 20, 2020

One primary objective of tuberculosis (TB) research is to discover how to treat people with the latent (or inactive) form of the disease so they don’t develop symptomatic TB.

Now, a breakthrough study from the Yerkes National Primate Research Center (YNPRC) and Southwest National Primate Research Center (SNPRC) has revealed how a specific combination of antibiotics could help.

For the study, the scientists created a latent infection in a group of rhesus macaques. They then treated half of the animals with a once-weekly combination of two antibiotics—isoniazid and rifapentine—for three months. The other half was untreated.

Numerous factors—including HIV infection, diabetes, aging or other diseases—can cause latent bacteria to become symptomatic and infectious again. To test whether the antibiotics had cleared bacteria from their lungs, both treated and untreated animals were infected with SIV (Simian immunodeficiency virus), which mimics HIV in humans. 

Of the animals that had no treatment for latent TB, 70 percent developed active TB after SIV infection. However, none of the animals that had the three-month course of antibiotics developed active TB after SIV infection, which suggests the treatment cleared the bacteria and prevented reactivation.

Because the current treatments for latent TB are lengthy, and many patients don’t finish them, a shorter treatment cycle like the one demonstrated in this study could be highly beneficial.

“The antibiotic treatment we used for this study is a new, shorter regimen the CDC recommends for treating humans with latent tuberculosis, but we did not have direct evidence for whether it completely clears latent infection,” explained Jyothi Rengarajan, PhD, Associate Professor of Medicine at Emory University and the Yerkes National Primate Research Center. “Our experimental study in macaques showing almost complete sterilization of bacteria after treatment suggests this three-month regimen sterilizes humans as well.”

The researchers at the NPRCs are working daily to find new potential treatments and cures for this infectious disease. Take a look at some of our other recent studies to learn about the progress we’ve made toward a TB-free world.

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

August 24, 2020

Note: The NPRCs will update this blog with our latest COVID-19 news.

Since beginning COVID-19 research in early 2020, NPRC researchers have made encouraging progress in efforts to better understand, diagnose, prevent and treat this novel disease. We’re committed to conducting and enabling research to end this global pandemic and to providing information so the public has ready access to our scientific results.

Our most recent COVID-19 news includes: 

  • April 13, 2021: Wisconsin NPRC scientists explore the shifts in the genetic material of COVID-19 to expand the viral genome sequence
  • February 25, 2021: Southwest NPRC helps people understand COVID-19 variants in this TX Biobytes podcast with virologist Dr. Jean Patterson
  • February 23, 2021: The New York Times features NPRC COVID-19 research in this story (Note: may require log in)

Below is even more information about our extensive and collaborative COVID-19 research:

Diagnostics:

Prevention:

Treatments:

Additional NPRC COVID-19 News:

Bookmark this page so you can easily return here for the latest NPRC COVID-19 research information. We’ve also compiled a list of resources here and provided links to previous NPRC COVID-19 news and national media stories here.

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.

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