Researchers at Texas Biomedical Research Institute (Texas Biomed) have made significant progress in the fight against tuberculosis (TB) and HIV co-infection. The team, led by Professor Smriti Mehra, Ph.D., has demonstrated that a promising TB therapy does not interfere with combined antiretroviral therapy (cART) used to treat HIV. 

A Critical Breakthrough 

Tuberculosis remains a global health concern, causing over 1.3 million deaths annually. For individuals with HIV, TB poses an even greater threat due to their compromised immune systems. The new therapy targets an immune system protein called IDO (Indoleamine-2,3-dioxygenase), which normally suppresses immune responses. 

How It Works 

By inhibiting IDO, the therapy aims to enhance the body’s ability to fight TB. This approach has already shown success in cancer treatments and has demonstrated improved control of TB when used alongside antibiotics. 

Safe for HIV Patients 

The study, conducted with nonhuman primates at the Southwest National Primate Research Center with both TB and simian immunodeficiency virus (SIV), revealed that the IDO inhibitor does not interfere with cART. This is crucial for developing a treatment that can help patients battling both HIV and TB. 

Next Steps 

Researchers plan to study how the inhibitor performs when used in conjunction with both antibiotics and cART together – the standard treatment regimen for patients with HIV and active TB. Long-term studies are also needed to confirm the absence of unintended side effects. 

Potential for Rapid Approval 

The IDO inhibitor is already FDA-approved for use in cancer patients, which could accelerate its potential approval for TB/HIV treatment compared to developing an entirely new drug. This research represents a significant step forward in addressing the challenges of TB and HIV co-infection, offering hope for more effective treatments in the future.

Scientists at Emory University have made an exciting discovery that could bring us one step closer to curing HIV. Their research, published in Nature Immunology, focuses on a special type of immune cell called CD8+ T cells. 

What’s the big deal?
The researchers identified a unique subset of CD8+ T cells in lymph nodes that are particularly effective at fighting simian immunodeficiency virus (SIV), which is similar to HIV in humans. These cells, called TCF1+CD39+CD8+ T cells, work differently from typical T cells but pack a powerful punch against the virus. 

Why is this important?
“Harnessing CD8+ T cell functions is imperative toward an HIV cure,” says Mirko Paiardini, PhD, Microbiology and Immunology division chief at the Emory National Primate Research Center. Currently, 39 million people worldwide live with HIV, and while existing treatments are effective in blocking the replication of the virus, they don’t eliminate the virus completely. 

How do these special T cells work?
These newly discovered T cells are unique because they: 

• Are better at controlling the virus 

• Reduce viral reservoirs (cells and places where the virus hides in the body) 

• Can maintain their effectiveness without getting “exhausted” 

• Have features that allow them to keep reproducing and fighting 

What’s next?
The Emory team plans to: 

• Study these T cells at different stages of infection 

• Explore how well they respond to potential HIV cure treatments 

• Investigate their effectiveness in other parts of the body beyond lymph nodes 

The bigger picture:
This research is part of a larger effort called ERASE HIV, which aims to develop innovative therapies to eliminate or control HIV without the need for lifelong medication. The team is also working with community organizations to share their findings and progress with those affected by HIV.  

While there’s still much work to be done, this discovery offers new hope in the ongoing battle against HIV and brings us closer to the possibility of a cure. 

The human immunodeficiency virus (HIV) remains a formidable challenge for medical researchers worldwide. While antiretroviral therapy (ART) has allowed individuals to manage HIV as a chronic condition and significantly improve their quality of life, certain aspects of the virus’s behavior still elude full comprehension. Among these mysteries lies the infiltration of HIV into the brain, a phenomenon with profound implications for individuals living with the virus. 

A groundbreaking study conducted at the California National Primate Research Center (CNPRC) is shedding new light on this intricate process. Led by Smita Iyer, an Associate Professor in the Division of Experimental and Translational Pathology at the University of Pittsburgh School of Medicine, led the study during her tenure as a CNPRC core scientist. The research offers insights into how HIV spreads within neural tissue and its implications for HIV-associated neurodegenerative disorders (HAND). 

Published in December 2023 in PLoS Pathogens, the study utilized nonhuman primate models to map the immune response to HIV in the brain. By focusing on immune cells known as CD4 T cells, the researchers uncovered the virus’s ability to penetrate neural tissue, thus highlighting its role in HAND. 

The significance of this research extends beyond HIV alone. As many individuals experienced with the cognitive impairments associated with COVID-19 can attest, viral invasion of the brain can have profound and enduring consequences. Nonhuman primate models, like those utilized at CNPRC, are instrumental in unraveling the mechanisms by which viruses breach the blood-brain barrier and persist within the central nervous system. 

Despite the success of ART in suppressing HIV replication in the bloodstream, some patients continue to experience chronic inflammation in the central nervous system. Known as Neuro-HIV, this condition underscores the virus’s unique ability to infiltrate the brain, disrupting neural function and potentially leading to cognitive decline. 

The CNPRC’s pioneering work in HIV and ART research has paved the way for advancements in understanding and combating the virus. From developing the simian immunodeficiency virus (SIV) model to conducting safety testing for crucial antiretroviral drugs, CNPRC’s contributions have been instrumental in the fight against HIV. 

Iyer’s study represents a continuation of CNPRC’s legacy, leveraging state-of-the-art technologies to track the progression of HIV within brain tissue. By elucidating the role of CD4 T cells in facilitating viral entry into the brain, the research provides valuable insights into the pathogenesis of Neuro-HIV. 

The findings of the study challenge conventional wisdom regarding the role of CD4 T cells in the body’s immune response to HIV. Rather than acting as guardians against viral invasion, these cells appear to serve as unwitting accomplices, aiding the virus in spreading throughout the body, including the brain. 

Looking ahead, Iyer and her team are focused on unraveling the complex interplay between different subsets of CD4 T cells during long-term HIV infection.  

By deciphering these intricate mechanisms, researchers aim to gain a deeper understanding of HIV’s impact on the central nervous system and develop targeted interventions to mitigate its effects. As they piece together the puzzle of Neuro-HIV, the quest for effective treatments and ultimately a cure continues unabated. 

Lyme disease, transmitted through tick bites, can leave patients with persistent neurological symptoms even after antibiotic treatment. However, a recent study conducted by Tulane University researchers offers hope to those suffering from long-term effects of the bacterial infection. 

Key Findings 

The study, published in Frontiers in Immunology, identifies fibroblast growth factor receptor (FGFR) inhibitors as a promising new approach to treating lingering neurological symptoms associated with post-treatment Lyme disease syndrome. These inhibitors  reduced inflammation and cell death in brain and nerve tissue samples infected with Borrelia burgdorferi, the bacterium responsible for Lyme disease. 

Research Approach 

Principal investigator Geetha Parthasarathy, PhD, led the study, treating nerve tissue with live or inactivated Borrelia burgdorferi followed by FGFR inhibitors. Results demonstrated a notable reduction in inflammatory markers and cell death, suggesting the potential efficacy of targeting FGFR pathways in addressing persistent neuroinflammation. 

Implications and Future Directions 

While further research is needed to translate these findings into clinical treatments, the study represents a significant advancement in understanding and potentially managing post-treatment Lyme disease syndrome. By focusing on underlying inflammation, researchers aim to develop treatments that improve the quality of life for patients affected by this debilitating condition. 

Supported by funding from the Bay Area Lyme Foundation and resources from the Tulane National Primate Research Center, this study opens new avenues for research and treatment development, offering renewed hope to Lyme disease patients grappling with lasting symptoms. 

In a groundbreaking stride toward combatting HIV, researchers have achieved a significant breakthrough in the quest for an effective treatment. Published in the prestigious journal Science on February 29, 2024, findings from a collaborative preclinical nonhuman primate study have illuminated a potential new avenue for managing HIV without the need for daily antiretroviral treatment (ART). 

Researchers at multiple institutions, including the Wisconsin National Primate Research Center and led by virologist James Whitney from Boston College and Harvard University, showcased the efficacy of a novel combination therapy involving an interleukin-15 superagonist therapy termed N-803 (marketed as Anktiva) along with broadly neutralizing antibodies (bNAbs). This promising therapy demonstrated the ability to enable the immune system to control HIV in individuals. 

Funded by the National Institutes of Health and the National Institute of Allergy and Infectious Diseases, the preclinical study conducted on rhesus macaques infected with chimeric simian-human immunodeficiency virus AD8 (SHIV-AD8) yielded encouraging results. The combination therapy of N-803 and bNAbs led to durable viral remission after discontinuation of antiretroviral therapy. 

Despite initial immune activation and transient viremia, the treatment showed only minor changes in the SHIV reservoir. Upon discontinuation of ART, approximately 70 percent of the treated macaques experienced long-term virus control for up to 10 months, marking a significant milestone in HIV research. 

These promising preclinical results have paved the way for the initiation of two Phase 1 clinical trials aimed at investigating the efficacy of N-803 and bNAbs in reducing viral loads in HIV-infected humans receiving antiretroviral treatment. One of the clinical trials, which includes an analytical treatment interruption to assess the impact of immunotherapies on post-therapy viral loads, is already underway at the Rockefeller University.  

Jon Levine, director of the Wisconsin National Primate Research Center (WNPRC), expressed optimism about the findings, highlighting the potential for widespread use of such therapies in HIV-infected patients. “This groundbreaking research not only offers hope for individuals living with HIV, but also represents a significant step forward in the global fight against the virus.” Levine said. 

As researchers continue to push the boundaries of medical science, the prospect of achieving sustained remission and ultimately finding a cure for HIV grows ever closer.  

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.