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.

In general, as humans, healthy aging impacts our cognitive and affective functions. Our cognitive capacity declines while our emotional lives become more positive and social relationships take a more central role.

The reasons for this are unknown, though scientists suspect it may be because humans have awareness of a limited lifetime. This could possibly lead to a greater interest in maintaining social relationships at the expense of the non-social world in the face of waning cognitive and physical resources.

However, a recent study conducted by researchers at California National Primate Research Center (CNPRC) found humans may be unique in this regard.

The scientists tested whether old rhesus macaques lost interest in non-social stimuli, collecting data from males and females between 4 and 30 years old. Each macaque was tested with a food puzzle outfitted with an activity monitor to evaluate their inclination to manipulate the puzzle in order to gain a food reward. The team found no indication older macaques were less interested in the puzzle than younger ones, nor were they less able to solve it.

These findings suggest there are no significant age-related changes in environmental exploration — at least in rhesus macaques — and indicate there is more research to be conducted to understand such social phenomena across species.

Could increasing just a single type of molecule in the brain alleviate anxiety? According to researchers at the California National Primate Research Center (CNPRC), it could indeed.

Anxiety disorders often emerge around adolescence and can continue to affect people for most of their lives. Researchers can now identify children who display an extreme anxious or inhibited temperament and determine that they are at risk to develop stress-related conditions as they transition to adulthood. However, little is known about how to effectively alleviate anxious symptoms.

CNPRC scientists recently conducted a study examining “dispositional anxiety”—the tendency to perceive many situations as threatening—in nonhuman primates. Researchers used an altered virus to boost levels of a molecule called neurotrophin-3 in the dorsal amygdala of juvenile rhesus macaques.

They found that this increase led to a decrease in anxiety-related behaviors, particularly behaviors associated with inhibition, a core part of the early-life risk for developing anxiety disorders in humans. Brain imaging studies of these animals found that neurotrophin-3 changed activity throughout the brain that contributes to anxiety.

Because current treatments work for only a subset of people and often only partially relieve symptoms, this finding provides hope for new methods of early-life intervention to treat people at risk for anxiety disorders, depression and related substance abuse.

Andrew Fox, an assistant professor in the UC Davis Department of Psychology and a researcher at the CNPRC, hopes that other scientists can further build on their research. The research team included a list of additional promising molecules for future investigation.

“We’re only just beginning,” noted Fox. “Neurotrophin-3 is the first molecule that we’ve been able to show in a nonhuman primate to be causally related to anxiety. It’s one of potentially many molecules that could have this effect. There could be hundreds or even thousands more.”

A new understanding of microbial processes is helping to reveal the cause of ulcerative colitis through the study of a nonhuman primate disorder, idiopathic chronic diarrhea (ICD).

ICD affects 3 to 5 percent of all captive macaque monkeys, and researchers believe wild macaques could be affected at similar rates. ICD is unresponsive to medical intervention and not caused by any particular pathogens.

California National Primate Research Center (CNPRC) scientist Amir Ardeshir, PhD, first began investigating the relationship between microbiomes and intestinal diseases like ICD in macaques—and ulcerative colitis in humans—when he learned of a human patient who had temporarily treated their ulcerative colitis by consuming the eggs of a parasite called Trichuris trichiura.

Ardeshir tried this patient’s home remedy in ICD-affected monkeys and discovered, astonishingly, that the parasite was an effective treatment in four out of five monkeys.

Now, in his latest study, Ardeshir and a team of researchers have found an interesting relationship between the Trichuris parasite and the monkeys’ microbiome—the community of trillions of microbes living on and in primates’ bodies.

The study found that treated monkeys had different microbial communities than healthy control subjects, making them particularly good at building the protective mucosal layer along the intestinal wall. This layer is key in protecting intestinal epithelium from pathogens.

The team of scientists then identified some of the specific bacteria occurring in cases of ICD using a new software called SAMSA2. This software-based approach revealed not only which bacteria were present in each monkey’s gut, but also provided information about what those bacteria were doing and how they might be interacting.

The researchers found a dramatically high number of “bacteria that are very notorious for mucin degradation,” Ardeshir noted. Mucins are glycoproteins which are necessary for the maintenance of the mucosal layer lining human and nonhuman primate intestines. Without it, the mucosal layer and gut bacteria can’t maintain a healthy relationship. Biopsies of human patients with ulcerative colitis show dysfunctional mucosal layers, suggesting this may be the source of irritation and inflammation in both ICD and ulcerative colitis.

Though the exact causes are still unclear, Ardeshir noted that this study brings the field much closer to a full understanding of these types of intestinal bacterial diseases.

Reviewed: June 2020

In 2018, wildfires tore across the state of California, leaving smoldering remains in their wake. These were some of the worst natural disasters on U.S. soil in recent years, and what’s worse, similar occurrences are becoming increasingly common.

If there’s any good to come from these phenomena, it’s that scientists are collecting data in the aftermath that could help reduce the effects of fires on humans and animals. This new research will add to the existing body of knowledge on the subject, including a study originally conducted in 2008 at the California National Primate Research Center (CNPRC). During the study, researchers found altered immunity and lung function in juvenile monkeys that were exposed as infants to wildfire smoke in 2008.

Lisa Miller, leader of the CNPRC Respiratory Diseases Unit, and her team recently tested lung function and blood samples from adult monkeys (now 10 years of age) that were originally exposed to the 2008 wildfire smoke. Their findings were consistent with the earlier study, suggesting that infant exposure to fine particles from fire leads to long term impairment of the respiratory and immune systems in adulthood. 

“The idea behind this is that if we detected any changes in the animals this information might translate as a biomarker that can be used for kids,” said Miller. “The ability of the animals to respond to a real pathogen was reduced. It was a surprise and somewhat disturbing.”

In 2018, smoke from the Butte County Camp Fire—which burned more than 700 square miles—reached the CNPRC, and about 2,000 animals and roughly 500 infant nonhuman primates were exposed for a period of more than 10 days. Because the fires came so close to the UC Davis campus where the CNPRC is located, researchers will once again be able to test the health effects of wildfire smoke on the center’s nonhuman primates. 

Examination of the results is still ongoing, but the additional data from this blaze will help Miller and team continue the search for causes, preventative measures and treatments for the damaging health effects of these massive wildfires.

Reviewed: June 2020

As recent news stories attest, measles is one of the most infectious diseases on Earth — and it affects more than just humans. Nonhuman primates are also at risk.

Although the CNPRC requires all employees and visitors to obtain measles vaccination or show proof of immunity, the center’s animals could still be at risk of outside contamination. Before 1996, the only vaccination protocols for nonhuman primates were based on protocols developed for humans, but these were not cost-effective, and primate facilities needed a better option.

This is why, since 1996, Kari Christe, DVM, has worked to test the safest and most efficient way to vaccinate the entire CNPRC rhesus macaque monkey colony. Her team’s work is also providing information to help other facilities make informed decisions on how to protect their animal colonies.

Christe and her veterinary team have made significant progress. Before this research began, many primate facilities did not have the resources to vaccinate their monkeys. But Christe and team have shown it is possible to protect rhesus macaques from measles in a cost-effective fashion using only half the recommended dose of a specific type of vaccine — the measles and canine distemper vaccine — in comparison to the measles, mumps and rubella vaccine used in humans. The new strategy will save research facilities, zoos and conservation organizations at least $3 per animal (there are nearly 4,000 animals at the CNPRC), based on the most recent estimates. 

With safer and more cost-effective vaccine protocols than ever before, Christe and CNPRC veterinarians are working their way toward protecting all nonhuman primates from measles at their facility and beyond. And this means those same animals will be able to participate in NPRC research studies focused on improving health for humans and animals alike.

Reviewed: June 2020