Autism Spectrum Disorder (ASD), which impacts communication and interaction abilities, affects 1 in every 54 children in the United States. In order to understand the biological basis of these types of human disorders, scientists must turn to translational animal models—research with animals that closely reflects the same processes in humans.    

Until now, there hasn’t been an effective way to identify which animals were ideal candidates for ASD research. But Kate Talbot, PhD, and her colleagues in the Neuroscience and Behavior Unit at the California National Primate Research Center (CNPRC) have optimized a screening tool—based on an ASD diagnostic tool used in humans—to do just that.  

ASD is classified by the National Institute of Mental Health as a developmental disorder that affects communication and behavior. It is a spectrum disorder, which means autism can present differently in symptoms and severity across individuals. This variability is part of what makes treatment of ASD more complicated. Rather than a primary treatment for ASD, doctors and patients have to work together to develop specific treatment programs.  

Talbot pointed out that studying disease biology directly in ASD patients is difficult in other animal models because they fundamentally lack the complex social cognitive abilities that are impaired in people with autism. But there is a subset of rhesus monkeys within the natural population illustrating low-social behavior similar to what is observed in humans with ASD. The difficult part is identifying enough of these animals early in their development to conduct the necessary translational research. 

Talbot and her team made a breakthrough in that area. The original macaque social responsiveness scale (mSRS) was a 36-item observation-based instrument similar to the Social Responsiveness Scale originally developed for human children. The mSRS was developed using a relatively small sample mostly composed of females, but due to the sample size and the fact that ASD is a particularly male-biased disorder (four males for every one female), the mSRS was difficult to translate to the human screening tool.  

Talbot and colleagues refined the mSRS by applying it to hundreds of male rhesus macaques across their development. They could then compare experimenter responses to the questionnaire directly to behavioral data collected on the animals throughout their lives. Now, the revised tool can determine with 96% accuracy which monkeys qualify as particularly low-social animals compared to their peers.   

“This instrument will be indispensable for advancing the field’s understanding of the developmental trajectory of core autistic symptomology in rhesus and other macaque monkeys, and it can be used as a primary outcome measure in fast-fail preclinical therapeutic testing efforts,” Talbot explained. 

Understanding autism and other neurological conditions is a primary goal of NPRC research. Find out more about our ASD-related studies by visiting this link.  

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.

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.

Cardiovascular disease is one of the leading causes of death in the United States, and it has many possible causes. One of the most well-known risk factors is hyperlipidemia, which presents as a high level of lipids, like triglycerides or cholesterol, in the blood. Scientists and doctors are still looking for effective ways to reduce cardiovascular risk from hyperlipidemia—and according to new research, fish oil may be part of the solution.

Recently, a team including Peter Havel, DVM, PhD, of UC Davis and the California National Primate Research Center (CNPRC) found that targeting a protein known as angiopoietin-like protein-3 (or ANGPTL3) could be helpful for managing cardiovascular disease.

In the study, the scientists gave 59 male rhesus macaques flavored, fructose-sweetened beverages daily in addition to their regular diet. A subset of macaques also received a whole fish oil supplement. The fructose supplementation allowed researchers to model symptoms of metabolic syndromes seen in humans, including insulin resistance and hyperlipidemia. This model also rapidly increased levels of triglycerides and certain lipoproteins in the blood, mirroring human risk factors for cardiovascular disease.

The results showed ANGPTL3 levels increased simultaneously with lipid levels in monkeys fed a high-sugar diet. It was also found that inhibiting the production of ANGPTL3 resulted in lower levels of several lipids and lipoproteins in circulation, which suggests the protein could be a helpful therapeutic target. What’s more, the researchers found that increases in the protein and lipids in the blood could be prevented if the animals were also provided with the fish oil supplement.

While the exact mechanisms remain unknown, Havel hopes to clarify in future studies exactly how components of fish oil influence ANGPTL3 production and circulating lipid levels. Understanding this could help scientists develop new interventions for the prevention and treatment of cardiovascular disease.

Heart health is incredibly important, which is why NPRC scientists are actively conducting research on cardiovascular diseases and treatments. Learn more about their breakthrough discoveries by visiting this link.

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

As scientists continue to make progress in the fight against human immunodeficiency virus (HIV), a recent discovery suggests that certain other microbes may play a role in how the body responds to vaccination.

According to researchers at the California National Primate Research Center (CNPRC) at the University of California, Davis (UC Davis), microbes living in the rectum could alter the effectiveness of experimental HIV vaccines.

Evidence from human and animal studies with other vaccines suggests supplements containing the bacteria Lactobacillus can boost antibody production, while treatment with antibiotics can hamper beneficial immune responses, according to Smita Iyer, assistant professor at the UC Davis Center for Immunology and Infectious Diseases and School of Veterinary Medicine. 

Iyer and her team specifically sought to learn if microbes living in the rectum and vagina—sites of HIV transmission—interacted with an experimental HIV vaccine similar to the HVTN 111 vaccine currently in early stage clinical trials in humans. According to Iyer, a vaccine that produces antibodies at the mucosal membranes where infection takes place is thought to be crucial.

The team studied rectal and vaginal microbes from rhesus macaques before and after they were vaccinated. While vaginal microbes did not show much difference before and after vaccination, rectal microbes did, with certain bacteria decreasing after vaccination. 

Furthermore, the amounts of the common gut bacteria Lactobacillus and Clostridia in the rectum correlated positively with the immune response. Animals with high levels of either Lactobacillus or Clostridia made more antibodies to certain HIV proteins, the researchers found. Prevotella bacteria showed the opposite pattern: High levels of Prevotella were correlated with weaker immune responses.

It’s not clear what the mechanism could be for some bacteria to boost local immune responses in a specific site in the body, Iyer said. However, targeting these bacteria could help scientists get the best possible performance out of vaccines that do not induce a particularly strong immune response, as is the case with HIV vaccines.

The NPRCs are actively conducting HIV/AIDS research across the country. Discover more ways our scientists are making progress against this disease in the ongoing pursuit of a cure.

Zika virus may be out of the headlines, but scientists are continuing to work on treatments and vaccines to address this serious threat to public health.

Now, an experimental vaccine against the virus has been shown to reduce the amount of virus in pregnant rhesus macaques and improve fetal outcomes. The study marks the first test of a Zika vaccine given before conception with exposure to the virus during pregnancy, said Koen Van Rompay, virologist at the California National Primate Research Center (CNPRC) at the University of California, Davis (UC Davis).

Zika virus infection of pregnant women is associated with a high risk of adverse fetal effects, including fetal death, microcephaly (small head) and other abnormalities, collectively termed congenital Zika syndrome. While no approved vaccine is currently available, the new study was designed to mimic a real-world scenario where women could be vaccinated months or years before becoming pregnant and be protected during pregnancy.

UC Davis researchers, alongside scientists from the National Institute of Allergy and Infectious Diseases (NIAI), injected female monkeys with candidate vaccine VRC5283. After vaccination, depending on their reproductive cycles, the female animals were housed with males and allowed to procreate. Thirteen vaccinated animals and 12 unvaccinated controls became pregnant. The investigators then exposed the pregnant animals to Zika virus at intervals representing first and second trimesters.

Two unvaccinated animals lost the fetus early in pregnancy due to Zika virus infection, but there was no early fetal loss in the vaccinated group. In addition, vaccinated females had less virus in their blood, and the virus persisted for a shorter duration after their exposure.

At the end of pregnancy, the researchers looked for Zika virus in tissues from the mothers and fetuses. It was found that 11 of 12 fetuses in the unvaccinated control group had detectable Zika virus RNA. However, no Zika virus RNA was detected in the 13 fetuses from the vaccinated group—suggesting that the vaccine prevented transmission of virus to the fetus. The results also indicate that VRC5283 may prevent mother-to-fetus transmission of Zika virus in humans, Van Rompay said.

The candidate vaccine is currently in trials, and results from the animal studies could help support the case for approving the vaccine.

Want to know more about the ongoing fight to eliminate Zika? Here are some additional ways NPRC scientists across the country are making progress against this disease.

Here’s a sobering statistic: one in every five American women and one in every 10 American men at the age of 45 are at risk of developing Alzheimer’s disease. Moreover, as the rate of the disease continues to increase and promising therapies tested in rodents fail in human subjects, the need for another option has become apparent.

Now, scientists at the California National Primate Research Center (CNPRC) have developed a monkey model of the earliest phase of Alzheimer’s. By selectively infusing protein fragments linked to the disease into the brain of middle-aged female rhesus monkeys, they have induced the earliest of the stages of Alzheimer’s, known as the synaptic phase, without neuron death. The researchers are focusing on middle-aged females, instead of the older populations previously studied, in hopes of identifying a treatment to stop the disease before irreversible degeneration occurs.

Some neurons, like those in the prefrontal cortex and hippocampus, are critically important for learning and memory and are more susceptible to the effects of Alzheimer’s than others. In a healthy brain, there is a delicate balance necessary for the cellular communication and plasticity necessary for learning—but in Alzheimer’s, this balance is compromised, leading to cognitive decline and possible neuron death.

The scientists believe that by instigating the synaptic damage, they have established a model of Alzheimer’s that isolates the synaptic phase before evidence of permanent damage.

Next, the researchers plan to examine ways of stopping Alzheimer’s progression before it reaches the degenerative phase. Primate models of the disease will greatly boost the capacity to outline an effective treatment plan for humans in the earliest phase of Alzheimer’s, prior to the worst symptoms and irreversible damage that results in dementia.

Interested in what else the NPRCs are doing to understand and improve brain health? Take a look at some related studies here.

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.