In medical research, discoveries come from persistence, creativity, and new angles.  

At the forefront of the endeavor to develop an HIV vaccine is Marie-Claire Gaudin, PhD, a professor at Texas Biomedical Research Institute and the Southwest National Primate Research Center. She has dedicated over a decade to crafting an innovative vaccine strategy that aims to halt virus as it enters the body. With support from NIH, including a recently awarded $3.8 million grant, Dr. Gauduin’s visionary approach is paving the way for a new era in HIV prevention. 

The Quest for an Effective HIV Vaccine 

The challenge posed by HIV is two-fold: its rapid spread through the body within days of infection and its ability to reach peak viral levels within two weeks. Traditional vaccine development has struggled to keep pace with the virus’s swift assault on the immune system. Enter Dr. Gauduin’s idea: why not intercept HIV at the very point of entry before it infiltrates cells and establishes its stronghold? 

Dr. Gauduin reflects on her “aha” moment, saying, “I had this idea as a postdoc. I thought it had to be naïve because nobody was talking about it. It was obvious and simple; I thought someone would have already done it.” Little did she know that her seemingly straightforward insight would set the stage for a paradigm shift in vaccine design. 

Unveiling the Strategy 

Dr. Gauduin’s novel approach is laser-focused on the mucosal epithelium—the inner lining of the vagina and rectum, where HIV is most likely to breach the body’s defenses. The vaccine sparks the production of antibodies specifically within these regions, strategically positioning them to thwart the virus’s advance.  

Additionally, it is engineered to engage the basal cells—the foundational building blocks of the lining. These basal cells are pivotal in renewing the epithelial layer, ensuring the body’s natural defense mechanisms remain fortified. The vaccine, nestled within the basal cells, is then passed on to new cells as the old ones die off, establishing an ongoing barrier against HIV entry. 

A Masterstroke in Prevention 

The vaccine’s potency is further enhanced by its composition as a live attenuated vaccine. Unlike its predecessors, it’s constructed from HIV’s genetic code, meticulously modified to remove harmful components. While live attenuated vaccines have been successful for diseases like smallpox and yellow fever, HIV’s propensity to mutate has thwarted previous attempts. 

From Lab Triumphs to Real-world Impact 

Dr. Gauduin’s vaccine exhibited impressive results in early trials involving nonhuman primates, and her sights are now set on expanding these promising outcomes. The following research phase entails a larger group of animals; a necessary step to establish safety and efficacy benchmarks before embarking on human clinical trials. As the vaccine progresses, Dr. Gauduin is also investigating alternative delivery methods to optimize efficiency, a crucial consideration for eventual mass immunization efforts.  

Every day, the seven National Primate Research Centers (NPRCs) conduct and enable collaborative research studies to improve human and animal health. For more than five years now, we’ve been sharing our latest news and scientific advancements with you via NPRC.org and @NPRCnews (X), and there’s more coming your way. 

To ensure the NPRCs provide the topics of most interest to our readers and followers, we looked back at your favorite stories to help us move forward. Your top interests span behavior and psychology, infectious disease and neuroscience and brain disorders research. We will continue to share news that represents what you have most enjoyed, and we will also bring you information that reflects the breadth and depth of research across the NPRC network.   

We appreciate our readers and followers, and encourage you to take another look at your favorite blogs about NPRC research, to share the information with your family, friends and colleagues, and to continue connecting with us via NPRC.org, @NPRCnews and, now, on the new NPRC LinkedIn account. Via these resources, you’ll always be able to access the latest news on NPRC research that is helping people across generations and around the world live longer, healthier lives.   

Behavior and Psychology 

1. The Effects of Wildfire Smoke Exposure in Early Pregnancy 

A study by California NPRC and UC Davis researchers investigated the effects of wildfire smoke exposure on infant monkeys during early pregnancy. The study found that exposure led to increased inflammation, reduced stress response, memory deficits and a more passive temperament in the monkeys. The findings suggest environmental changes during pregnancy can have lasting effects on offspring.  

Infectious Disease 

2. A Deadly Relationship: Stopping the Progression of Tuberculosis in HIV Patients   

Researchers at the Southwest National Primate Research Center have discovered chronic immune activation in the lungs plays a crucial role in the progression of tuberculosis (TB) and HIV co-infection. This dysfunction hampers the body’s ability to fight off infections. The study suggests the need to develop treatments targeting chronic immune activation alongside antiretroviral therapy (ART). TB and HIV are global pandemics that reinforce each other, affecting a significant portion of the world’s population. The findings offer hope for improved treatment strategies in the next decade. 

3. New Possible Correlation Between Lyme Disease and Lewy Body Dementia  

At Tulane National Primate Research Center, researchers discovered intact spirochetes of Borrelia burgdorferi, the bacterium that causes Lyme disease, in the central nervous system of a 69-year-old woman who received multiple rounds of antibiotic treatment. The presence of this bacterium coupled with her persistent neurological decline raises the possibility of a correlation between Lyme disease and Lewy body dementia. This finding highlights the bacterium’s persistence despite targeted therapy and emphasizes the need for further research to comprehend its role in severe neurological conditions. 

4. Are DNA Vaccinations a Perennial Answer to the Flu?  

Researchers at the Washington National Primate Research Center are developing a universal flu vaccine that could protect against all strains of the influenza virus. Using a DNA vaccine administered through the skin, the team has achieved promising results in macaques, providing 100% protection against a previous flu virus. This approach could eliminate the need for annual flu shots and be quickly deployed during pandemics. The researchers believe this technology could also be effective against other viruses and outbreaks. 

Neuroscience & Brain Disorders 

5. Past Social Experiences May Affect Brain’s Response to Oxytocin

A study at the Emory (formerly Yerkes) National Primate Research Center and Emory University showed the response of neurons to oxytocin, a chemical involved in social bonding, can vary based on an individual’s past experiences. Using female prairie voles, the researchers examined the nucleus accumbens, a brain region related to pair bonding. They found that oxytocin reduced neuron firing before bonding and increased it afterward, when triggered. The study also revealed a connection between oxytocin signals and endocannabinoids, affecting defensive interactions. These findings provide insights into how prior experiences influence oxytocin’s impact on brain circuits. 

6. NPRC Study May Have Found Link That Causes Anxiety and Depression  

Researchers at the Wisconsin National Primate Research Center and the University of Wisconsin-Madison have discovered brain pathways in juvenile monkeys that could contribute to anxiety and depression later in life. By studying the connections between specific brain regions, they found a correlation between synchronization and anxious temperament. These findings may lead to better treatment approaches and help identify gene alterations associated with anxiety. 

7. The Drinking Gene: Could Alcoholism Be Inherited?  

Research conducted at Oregon National Primate Research Center has identified a gene, GPR39, as a potential target for developing medication to prevent and treat alcoholism. By modifying protein levels encoded by this gene in mice, the researchers observed a significant reduction in alcohol consumption. They also found a link between alcohol and the activity of this gene. The study draws attention to the importance of cross-species approaches to identify drugs for treating alcohol use disorder. Further investigations are under way to determine if the same mechanism applies to humans. These findings offer potential insights for developing drugs to address chronic alcoholism and mood disorders. 

The battle against COVID-19 has been relentless, and scientists at Emory University and researchers from collaborative institutions worldwide are leaving no stone unturned in their quest for innovative treatment options. In an exciting breakthrough, researchers at Emory’s NPRC and their colleagues have delved into the intricate world of type 1 Interferon (IFN-I) signaling, a key player in our body’s defense against infections. Their groundbreaking study, conducted with nonhuman primates, offers a fresh perspective on combating SARS-CoV-2, and paves the way for potential new treatments for COVID-19. 

The Defender: Type 1 Interferon 

Senior author, Mirko Paiardini, PhD, and his team focused on understanding the role of IFN-I in SARS-CoV-2 infections. IFN-I is like the first responder in our body’s defense mechanism, acting swiftly to thwart viral replication when an infection is detected. This study, a first in nonhuman primates, sheds light on how tweaking IFN-I signaling can impact viral replication and the progression of COVID-19. 

The Balancing Act: IFN-I’s Double-Edged Sword 

The findings of the Emory University study illuminate a delicate balance in the fight against COVID-19. While early IFN-I responses are crucial for containing SARS-CoV-2, an excess of IFN-I signaling can lead to hyperinflammation in the body, contributing to severe disease. This discovery underscores the importance of timely intervention to prevent excessive inflammation, a primary driver of severe COVID-19 cases. 

Dr. Paiardini, Division Chief of Microbiology and Immunology, Professor of Pathology and Laboratory Medicine, and Co-Director at the Emory Center for AIDS Research, emphasizes the significance of this balance and the need to fine-tune the body’s immune response to combat the virus effectively. 

The Experiment: IFNmod to the Rescue 

Researchers used a modified version of interferon, aptly named IFNmod, in rhesus macaques before and during acute SARS-CoV-2 infection to modulate IFN-I signaling. The results were nothing short of remarkable. IFNmod treatment weakened antiviral and inflammatory gene expression, leading to lower levels of inflammatory cytokines in the lower airways. This reduction in inflammation correlated with reduced lung pathology.  

“We were also surprised to find IFNmod treatment had a profound effect on SARS-CoV-2 viral loads, with a 3,000-fold reduction in viral loads in the lower airways of treated animals,” says co-first author Elise Viox.  

Emory University’s groundbreaking research into modulating type 1 Interferon signaling offers hope in our battle against COVID-19. By striking the delicate balance between immune response and inflammation, we’re closer to effective treatments for this tenacious virus.  

The Influence of Social Status on Early Social Development: Insights from Maturing Visual Pathways

 Forming infant-caregiver bonds is critical to social and neural development during infancy. However, the underlying brain pathways supporting infant attention to others’ eyes have remained largely unknown. Recent groundbreaking research conducted at the Emory National Primate Research Center (EPC) and the Marcus Autism Center sheds light on the development of eye contact behaviors in infant rhesus macaques and their influence on brain growth. This research not only has the potential to reveal early neurobehavioral markers of social disability but also provides insights into the impact of social status on these developmental processes.

“For both humans and macaques, learning to engage with the eyes of others during infancy is a critical social skill in typical neurodevelopment,” says senior author Mar Sanchez, Ph.D. Exploring the brain regions and environmental factors that contribute to this behavior can enhance our understanding of its emergence and role in primates’ social development.

Studying Infant Macaques

The research team conducted a study involving male infant macaques, measuring their eye contact behaviors through eye-tracking tools while showing them videos of other macaques. Resting-state functional MRI (rs-fMRI) scans were also taken to analyze connectivity within the occipital and temporal cortices, which are involved in visual perception and social processing.

The researchers collected data from two weeks to six months old at regular intervals. This unique longitudinal dataset allowed them to observe changes in the connectivity patterns between the occipital and temporal cortices over time. They discovered that the most significant changes occurred during the first three months of life, which is analogous to humans’ first year of life.

Importance of Brain Connectivity and Influence of Social Status

Infants with stronger connections between the brain areas responsible for visual processing (primary visual areas) showed a greater tendency to make eye contact with other monkeys earlier than infants with weaker connections. The study also revealed that social status impacted the relationship between brain maturation and eye contact. Low-ranking infants displayed a stronger association between the development of visual pathways and eye contact compared to their high-ranking counterparts. This suggests that low-ranking infants may have adapted brains that facilitate early identification of faces and expressions, enabling them to navigate social interactions more effectively.

Implications for Human Development

Aiden Ford, the first author and a Ph.D. candidate in Neuroscience at Emory, highlights the influence of social status on the development of the social brain, even in the earliest postnatal months. This research provides unique insights into brain and behavior development dynamics at both the group and individual levels. It also raises the possibility that early exposure to adversity may accelerate biological, brain, and social development.

The research group plans to conduct further studies mapping the development of social behaviors and social brain regions in infant macaques. The amygdala, a critical part of emotional processing, will be a particular focus. Additionally, the effects of infant social status will continue to be investigated, providing a deeper understanding of how social factors shape neural development.

While current HIV treatment reduces viral load, or the amount of HIV in the blood, there is no cure for the disease. Antiretroviral therapy (ART) involves either taking a shot or a daily pill. Then a test can’t often detect HIV because the viral load becomes so low. Unfortunately, skipping a treatment, even now and then, gives the remaining virus a chance to multiply rapidly, weaken the immune system and cause illness. 

A truly effective treatment for chronic HIV infection would eliminate these residual infected cells, known as the HIV reservoir. A drug called N-803, developed by ImmunityBio, Inc., has the potential to be such a therapeutic. N-803 is now in clinical trials for treating non-muscle invasive bladder cancer that does not respond to standard therapy. The drug received Fast Track and Breakthrough Therapy designations in 2017 and 2019, respectively, from the U.S. Food and Drug Administration (FDA) for this cancer based on its demonstrated activity as a compound that stimulates the immune system. 

Shelby O’Connor, a professor of pathology and laboratory medicine at the University of Wisconsin–Madison and a scientist at the Wisconsin National Primate Research Center, recognized that N-803 might also have the potential to treat HIV. She and her research team evaluated this drug’s effectiveness in the context of various immune states and concurrent therapies in simian immunodeficiency virus (SIV) models, using both rhesus and cynomolgus monkeys. 

The researchers discovered overall that primates with low viral copies before N-803 treatment improved their ability to kill SIV during treatment. Primates with higher viral load before treatment showed chronic activation of T-cells, resulting in immune “exhaustion” and leaving these immune cells that target SIV unable to fight viral infection even with the treatment. 

This NIH-funded research suggests the drug is most effective in hosts with a natural pre-existing immunological ability to control SIV replication. This aligns with N-803’s known ability to increase the proliferation of both natural killer cells and T cells in hosts with higher-functioning immune systems. 

The O’Connor lab plans to continue investigating how N-803 may react differently in individuals that control HIV and SIV compared to settings where the virus is not controlled.

HIV, human immunodeficiency virus, destroys CD4 cells, also known as helper T cells, in the immune system. Without these cells, bodies have a hard time fighting off various diseases. While there is currently no cure for HIV, people now live long and fulfilling lives with it when treated medically.

Long-term medical treatment isn’t ideal, however, making the fight far from over. Researchers are constantly looking for ways to develop new treatments. One reason HIV is hard to eliminate is its ability to escape drug treatment by hiding in the body, including in the lymph nodes and spleen.

Infected cells hole up in an area of the lymph tissue called the B cell follicles. Immune cells, including T cells and natural killer (NK) cells, whose job is to kill virally infected cells, are generally unable to reach the B cell follicles, making them a safe space for the virus.

Using findings from a previous study published in the Proceedings of the National Academy of Sciences in 2017 focused on B cells, a research team at Emory National Primate Research Center (EPC) studied rhesus macaques with chronic SIV infection.  

“Infiltration of these highly cytotoxic NK cells in the B cell follicles has never been shown before during chronic HIV/SIV,” says senior author Vijayakumar Velu, Ph.D., an assistant professor in the Division of Microbiology and Immunology at the EPC. “This study has implications for developing new cure strategies for HIV, as these cells traffic to B cell follicles during controlled infection,” says co-author Rama Amara, Ph.D.

While more research is needed before introducing new treatments to humans, it’s a huge step in ultimately finding a cure for those living with HIV.

Covid-19 is a highly contagious and quickly spread disease caused by SARS-CoV-2. Since its discovery in 2019, researchers have remained dedicated to creating a vaccination for people of all ages. While many people with Covid-19 have mild symptoms, others can become highly ill as the disease attacks the lungs and respiratory systems.

In late 2022, the CDC expanded the use of vaccines for children ages six months to 5 years old. The CDC states, “The vast majority of children in this age group have not received any doses of a COVID-19 vaccine. CDC is working to increase parent and provider confidence in COVID-19 vaccines and improve uptake among the 95% of children who are not vaccinated or have not completed the COVID-19 vaccine primary series.”1

A new study from the California National Primate Research Center, UNC-Chapel Hill, and Will Cornell Medicine, determined two-dose vaccines protect against lung disease in rhesus macaques one year after they were vaccinated as infants.

Researchers immunized two groups of eight infant rhesus macaques at the CNPRC at two months of age and again four weeks later.

Each animal received one of two vaccine types: a preclinical version of the Moderna mRNA vaccine or a vaccine combining a protein with a potent adjuvant formulation. One year later, the animals received a high-dose challenge with a SARS-CoV-2 variant to test their immune responses. Both proved successful in protecting against lung disease implying the vaccines are safe and highly effective when given to young infant macaques and may reduce the need for frequent boosters in young children.

Young infants are one of the most vulnerable populations regarding Covid-19. “This study emphasizes the need to get human infants immunized against SARS-CoV-2 as much as possible, as the benefits are clear and long-lasting. It also highlights the value of animal models in infectious disease research,” said Koen Van Rompay, co-author of the study. 

The immune system has long been touted as the body’s primary defense against invading viruses, with the understanding that a strong immune response swiftly knocks out an infection while a weak one allows it to linger, leading to prolonged disease or even death.

Now, researchers at Tulane University are looking at an entirely different system—the body’s ability to use nutrients at a cellular level — to predict disease response and severity.

Tulane immunologist Clovis Palmer, PhD, studies metabolic changes resulting from viral infections. In a literature review published in Nature Metabolism, Palmer analyzed a body of evidence that looked at the metabolic changes that occur in cells when viral invaders, such as HIV, hepatitis B, or SARS-CoV-2, pose a threat.

Palmer concluded that the way in which cells, even non-immune cells, use nutrients in the presence of a viral pathogen can determine disease outcome and severity in the earliest stages of infection, or even long after the pathogen leaves the body.

Certain molecules on the surface of a cell determine how nutrients are used. These allow nutrients like glucose and fat to facilitate energy production or, if necessary, mount an offense against invading pathogens. Under these conditions, nutrients strengthen and bolster the cell. But viral pathogens can also hijack these surface molecules to gain entry into the cell and then use the nutrients to replicate.

“Whether nutrients are used to strengthen and defend the cell or are hijacked by the virus depends on conditions in the host like older age, nutritional status and obesity,” Palmer said. “We saw that these were all significant risk factors for the worst outcomes of COVID but didn’t really know what was driving it.”

Understanding how cells use nutrients in the presence of viral pathogens at the earliest states of infection is key to the development of treatments that can strengthen the cell, not the virus. While most antiviral medications take aim at the virus, Palmer seeks to prevent or lessen disease by keeping the nutrients on the cell’s side.

Palmer is working with Jay Rappaport, PhD, director of the Tulane National Primate Research Center and professor of microbiology and immunology at the Tulane University School of Medicine, on rewiring metabolic response in nonhuman primate models of COVID and HIV to prevent and treat long-term symptoms.

“We know that when metabolism is impaired, there is increased susceptibility to infection,” said Rappaport. “Modulating the metabolic response has vast implications for all infectious diseases, from optimizing immunity to mitigating the effects of aging, autoimmunity, and other drivers of disease.”

Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus. While the disease is relatively new, researchers are now studying its long-term effects. Some people with COVID-19 experience little to no symptoms, while others continue to experience fatigue, respiratory and neurological symptoms.

According to a recent report, eighty percent of individuals hospitalized for COVID-19 reported neurological symptoms. Because of this, researchers from the California National Primate Research Center at the University of California, Davis, decided to explore this complex issue further. The findings reveal significant neuron damage and inflammation in rhesus macaque monkeys within a week of infection.

In addition, the study unveiled an exacerbated effect in older rhesus macaques and those with Type 2 diabetes. The virus spread further in the brain, by traveling through the nose along the olfactory nerve, in aged animals and affected their memory and cognition causing particular concerns about potential spikes in neurodegenerative diseases in humans.

John Morrison, professor of neurology at UC Davis and director of the CNPRC, states, “In the aged monkeys, in particular, the virus is infecting neurons in regions known to be highly vulnerable to Alzheimer’s disease.” 

The researchers plan to continue to study the brain post-infection to examine the extent and nature of brain damage underlying the long-term neurological complications of COVID-19 to help doctors better understand how to help humans affected by the disease.

Approximately 30,000 cases of Lyme disease are reported to CDC every year. Lyme disease transmits the Lyme disease-causing bacteria to humans through the bite of infected ticks with symptoms including fever, headaches, tiredness, and a skin rash. If Lyme is left undetected, the infection can infect the body’s joints, heart, and even nervous system. These patients can suffer from severe neurological issues, significantly diminishing their quality of life.

While antibiotics can effectively treat most cases that are detected early,, undetected infections become harder to eradicate and can cause more prolonged-term effects on people. Research about these neuroinflammation symptoms associated with Lyme disease is limited and evolving. 

 Recently, researchers at the Tulane National Primate Research Center discovered remnants of B. burgdorferi, the bacteria causing Lyme disease, may contribute to inflammation in the nervous system. In fact, these remnants can be more inflammatory (and can also cause cell death) than live bacteria, according to the trials using nonhuman primates. 

While antibiotics kill most intact bacteria in organs, some individuals cannot completely rid themselves of the remnants. Geetha Parthasarathy, Ph.D., assistant professor of microbiology and immunology at the Tulane National Primate Research Center, explains, “As neuroinflammation is the basis of many neurological disorders, lingering inflammation in the brain due to these unresolved fragments could cause long-term health consequences.”