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.

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.

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.

Children born to HIV-positive mothers are susceptible to contracting the disease themselves, but scientists at Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University (OHSU) have new evidence suggesting that newborn infection may be entirely preventable.

The researchers successfully demonstrated, in a non-human primate model, that a single dose of an antibody-based treatment given after virus exposure can prevent HIV transmission from mother to baby, provided that dose is given at the correct time. 

The study found that rhesus macaque newborns did not develop the monkey form of HIV (known as SHIV), when they received a combination of two antibodies 30 hours after being exposed to the virus. This is the first time a single dose of broadly neutralizing antibodies given after viral exposure has been found to prevent SHIV infection in nonhuman primate newborns.

However, when the antibody treatment was delayed until 48 hours after exposure, half of the baby macaques developed SHIV, even when given four smaller doses of the same antibody. 

Previous research by this group has shown that four doses of antibodies started 24 hours after exposure also prevented SHIV infection, and the current ONPRC study suggests that a three-week course of antiretroviral therapy given after virus exposure could also prevent HIV transmission to newborns.

“These promising findings could mean babies born to HIV-positive mothers can still beat HIV with less treatment,” said Nancy Haigwood, PhD, ONPRC director and a professor of pathobiology and immunology at the OHSU School of Medicine.

Antibodies aren’t toxic and can be modified to last a long time in the body, which reduces treatment frequency. This means antibody treatments may also help prevent negative side effects from the drug combination currently given to infants born to HIV-positive mothers.

Next, ONPRC scientists plan to see if different antibodies, or a combination of antibodies and antiretroviral therapy, could be even more effective. They also hope to find out whether the antibodies actually eliminate HIV or only prevent it from replicating.combination. This suggests that there is a 30-hour limit for the successful use of antibodies to prevent HIV transmission to newborns.

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.

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.

Scientists have made one more step toward the treatment and cure of multiple sclerosis (MS) by developing a compound that successfully promotes the regeneration of the protective myelin sheath around nerve cells.

In a recent study, scientists at the Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University (OHSU) described successfully testing the compound in mice, and they have already started to apply it to a rare population of macaque monkeys who develop a disease that is similar to MS in humans.

“I think we’ll know in about a year if this is the exact right drug to try in human clinical trials,” said senior author Larry Sherman, PhD, an OHSU professor in the Division of Neuroscience at the primate center. “If it’s not, we know from the mouse studies that this approach can work. The question is, can this drug be adapted to bigger human brains?” 

The discovery arrives after more than a decade of research following a 2005 breakthrough by Sherman’s lab. In that study, scientists discovered that a molecule called hyaluronic acid (HA), accumulates in the brains of patients with MS. The researchers then linked this accumulation of HA to the failure of cells called oligodendrocytes (which generate myelin) to mature. 

Myelin forms a protective sheath covering each nerve cell’s axon—the threadlike portion of a cell that transmits electrical signals between cells. Damage to myelin is associated with MS, stroke, brain injuries and certain forms of dementia like Alzheimer’s disease. Delay in myelination can also affect infants born prematurely, leading to brain damage or cerebral palsy. 

Other studies led by the Sherman lab have shown that HA is broken down into small fragments in multiple sclerosis lesions by enzymes called hyaluronidases, and these fragments send a signal to immature oligodendrocytes to not turn on their myelin genes. 

There is currently no cure for MS, but an international team of researchers led by OHSU has been working to develop a compound that neutralizes the hyaluronidase in the brains of patients with MS and other neurodegenerative diseases. This will ideally revive the ability of progenitor cells (descendants of stem cells that differentiate, or change, into specific cell types) to mature into myelin-producing oligodendrocytes and regenerate myelin sheath. 

The ONPRC macaque study describes a modified flavonoid—a class of chemicals found in fruits and vegetables—that does just that. The compound, called S3, reverses the effect of HA and promotes functional remyelination in mice. 

“It’s not only showing that the myelin is coming back, but it’s causing the axons to fire at a much higher speed,” Sherman said. “That’s exactly what you want functionally.”

The next phase of research involves testing, and possibly refining, the compound in macaque monkeys who carry a naturally occurring version of MS called Japanese macaque encephalomyelitis. The condition, which causes clinical symptoms similar to multiple sclerosis in people, is the only spontaneously occurring MS-like disease in nonhuman primates in the world. 

Researchers at the ONPRC and other NPRC locations are consistently making breakthrough discoveries to help treat and eradicate MS and other neurological diseases. Learn more about the latest findings here.

Is it possible for consciousness to be controlled through the brain? And if so, what implications could this have for people with serious brain disorders or conditions, like comas?

As it turns out, a small amount of electricity delivered at a specific frequency to a particular point in the brain will wake a nonhuman primate out of deep anesthesia, according to a study by a team led by researchers at the Wisconsin National Primate Research Center (WiNPRC) at the University of Wisconsin-Madison (UW).

Macaques put to sleep with general anesthetic drugs commonly administered to human surgical patients, propofol and isoflurane, were revived and alert within two or three seconds of applying a low electrical current.

“For as long as you’re stimulating their brain, their behavior — full eye opening, reaching for objects in their vicinity, vital sign changes, bodily movements and facial movements — and their brain activity is that of a waking state,” said Yuri Saalmann, UW-Madison psychology and neuroscience professor. “Then, within a few seconds of switching off the stimulation, their eyes closed again. The animal is right back into an unconscious state.”

Mice have been roused from light anesthesia before with a related method, and humans with severe disorders have improved through electric stimulation applied deep in their brains. The new study, however, is the first to pull primates in and out of a deep unconscious state.

In the study, the scientists focused on a spot deep in the core of the brain called the central lateral thalamus. Lesions in that area of the human brain are linked to severe consciousness disruptions, such as comas.

As the macaques moved from unconscious to conscious states, the researchers observed the central lateral thalamus stimulating parts of the cortex, or the outer folds of the brain. In turn, the cortex influenced the central lateral thalamus to keep it active, forming a loop—or an engine—of sorts.

Achieving this manipulation of consciousness in the brain required precisely stimulating multiple sites as little as 200 millionths of a meter apart simultaneously, as well as applying bursts of electricity 50 times per second. The researchers noted that designing and delivering electrical stimulation with such precision gives them hope that their approach could be used to help patients dealing with many types of abnormal brain activity.

 “We can now point to crucial parts of the brain that keep this engine running and drive changes in the cerebral cortex that affect your awareness, the richness of your conscious experience,” explained Saalmann.

The inner workings of the brain are complex and have yet to be fully unraveled, but scientists at the NPRCs are making daily progress in helping us to understand this fascinating and crucial organ. You can learn more about the other NPRC neuroscience 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

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.

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.