How NPRC Research Accelerated HIV Advances From 2020–2025

From breakthroughs in prevention to promising treatments, the National Primate Research Centers (NPRCs) have played a crucial role in advancing HIV research. Working with nonhuman primates, the closest biomedical model to humans, NPRC researchers have tackled some of HIV’s biggest challenges: viral persistence, brain invasion, co-infections and the limits of current therapies. Together, these discoveries mark some of the most significant progress toward long-term remission and potential cures in decades.

Strengthening Vaccines and Early Prevention

NPRC advances include efforts to block infection before it starts. Researchers at the Emory National Primate Research Center (ENPRC) at Emory University showed that an Env-plus-Gag HIV vaccine regimen in rhesus macaques provided durable protection from SHIV, the simian version of HIV, even when neutralizing antibody levels were low. This finding expanded thinking around the types of immune responses a successful vaccine must generate.

At the same time, Oregon NPRC scientists found that leronlimab, a monoclonal antibody that blocks the CCR5 co-receptor, effectively prevented SHIV infection in nonhuman primate models. Already tested in human studies for viral suppression, the antibody also showed promise as a PrEP-style preventive option.

Targeting HIV’s Hidden Reservoirs

Because HIV hides in tissues the immune system can’t easily reach, several NPRC studies focused on uncovering and disrupting these viral reservoirs. ENPRC scientists discovered that the anti-inflammatory molecule IL-10 helps HIV-infected cells survive in lymph nodes. Blocking IL-10, alongside antiretroviral therapy (ART), reduced the number of infected reservoir cells, marking an important step toward weakening HIV’s stronghold.

Researchers at Emory NPRC also identified specialized follicle-infiltrating NK cells capable of entering B-cell follicles in lymph nodes, one of HIV’s most protected hiding places. These findings point toward future therapies that could guide immune cells directly into viral reservoir sites.

Additional “shock and kill” studies at Wisconsin NPRC showed that both latency-reversing drugs and checkpoint inhibitor combinations can reactivate dormant virus while nonhuman primates are on ART, laying groundwork for strategies that flush HIV out of hiding.

Immune-Based Therapies Move Toward Functional Cure

By 2024, several NPRC collaborations delivered results that brought the field closer to long-term remission without lifelong treatment. A landmark study testing N-803 (IL-15 superagonist) plus broadly neutralizing antibodies achieved long-lasting viral control in most SHIV-infected macaques even after ART was stopped. The findings have now progressed to early-phase human clinical trials.

Emory NPRC researchers also identified a particularly potent subset of CD8⁺ T cells (TCF1⁺CD39⁺) that excel at controlling SIV and resisting exhaustion. The importance of these cells has been confirmed also in people with HIV and may become powerful tools in future immunotherapies.

Understanding HIV in the Brain

Another major advancement came from California NPRC, where researchers discovered how HIV enters and persists in the brain. Their work showed that CD4 T cells can inadvertently carry virus into neural tissue, helping explain why HIV-associated neurocognitive disorders persist even when ART is effective.

Addressing Co-Infections and Real-World Treatment Needs

HIV rarely exists in isolation. In 2025, Texas Biomed and the Southwest NPRC demonstrated that a promising tuberculosis therapy did not interfere with combined antiretroviral therapy (cART) used to treat HIV, supporting its safe use in people co-infected with HIV and TB. Because the drug is already FDA-approved for use in cancer patients, it could accelerate potential approval for TB/HIV treatment compared to developing an entirely new drug.

A Path Toward Remission

Building on these advances, Emory NPRC researchers reported one of the strongest signals yet that a functional cure for HIV may be achievable. In a stringent SIV model, a targeted combination therapy, blocking two negative regulators of the immune system, IL-10 and PD-1, enabled durable control of viral rebound in 9 of 10 nonhuman primates for six months after ART ended, an unprecedented result that strengthens the path toward future human trials. This is a direct proof of concept that the immune system can be harnessed with immune-based interventions to control HIV.

The Bottom Line

Between 2020 and 2025, NPRC research meaningfully advanced the HIV landscape. Through innovative vaccine approaches, better understanding of persistence, targeted immune strategies and real-world treatment insights, the NPRCs have laid essential groundwork for an era in which long-term HIV remission, and ultimately a cure, becomes an attainable goal.

A New Hope for Cardiovascular Patients

University of Wisconsin–Madison NPRC scientists have made a significant leap in heart surgery innovation: they’ve developed bioengineered arteries using stem cells that could one day transform how doctors perform vascular bypass procedures.

Why New Arteries Are Needed

Currently, when patients need small-diameter blood vessels for procedures like coronary bypass surgery, surgeons must use vessels from another part of the patient’s body. This approach is invasive, can be limited by the patient’s health, and is not always possible. Donor vessels are another option, but they often face immune rejection.

The Science Behind Bioengineered Grafts

The research team created a new kind of “off-the-shelf” artery by:

• Using pluripotent stem cells to generate arterial endothelial cells (AECs), the cells that line blood vessels.
• Attaching these cells to a small synthetic graft made of ePTFE (the same material as Teflon), which is specially coated with proteins inspired by mussels to help the cells stick.
• Testing the grafts in Rhesus macaques, a primate model similar to humans.

What Did They Find?

The scientists compared different types of grafts:

• Uncoated synthetic grafts
• Grafts lined with normal (wildtype) AECs
• Grafts lined with AECs modified to avoid immune detection (major histocompatibility complex (MHC) double knockout)

Surprisingly, the (MHC) double knockout grafts failed half the time, possibly due to innate immune cells (natural killer cells) attacking them. The wildtype grafts, however, worked well for six months, and the host’s own cells repopulated the graft, supporting long-term success.

What’s Next?

This study is a promising step toward creating ready-to-use, stem cell-based vascular grafts for heart and vascular surgeries. If successful in future human trials, these grafts could:

• Reduce the need for invasive vessel harvesting
• Expand surgical options for patients with limited vessel availability
• Lower the risk of immune rejection

The Big Picture

As Dr. Samuel Poore, a co-author, explains: “This is an exciting, collaborative project with the potential to be a true bench to bedside advancement.”

A new study on placental gene therapy in rhesus macaques has shown promising results that could lead to improved outcomes for human pregnancies affected by placental insufficiency. The research, conducted by scientists Dr. Helen Jones, from the University of Florida, and Dr. Jenna Schmidt, University of Wisconsin—Madison and Wisconsin National Primate Research Center, focuses on developing a treatment for placental insufficiency. 

Placental insufficiency is a significant concern in human pregnancies, underlying the majority of stillbirths or resulting in low birth weight and extended stays in neonatal intensive care units. The condition can have lasting effects on health throughout their lifespan, potentially leading to cardiovascular disease and neurocognitive developmental issues later in life. 

The researchers used a polymer-based nanoparticle loaded with a plasmid encoding the human IGF-1 protein, which is crucial for normal placental development. This approach builds on Dr. Jones’ 13 years of previous research supported by the NIH Eunice Kennedy Shriver National Institute for Child Health and Development. 

Key findings from the study include: 

• Successful expression of the IGF-1 transgene only in the placenta 

• No negative immune responses from the mother or fetus 

• Transgene expression lasting up to 10 days after treatment 

While the current study involved direct injection into the rhesus macaque placenta, future research aims to refine the delivery method for potential human applications. The next steps include: 

• Delivering nanoparticles via the mother’s circulation 

• Exploring multiple treatments throughout pregnancy 

• Measuring the impact on both mother and fetus through birth 

The ultimate goal of this research is to improve placental function, extend pregnancies, and result in healthier babies and adults. As the study progresses, it brings hope for a potential treatment for placental insufficiency, a condition that currently has no available therapies. 

This innovative research represents a significant step forward in addressing pregnancy complications and improving long-term health outcomes for both mothers and children. 

A study led by researchers from the University of Wisconsin—Madison and Mayo Clinic has demonstrated the potential of stem cell therapy in treating congenital heart defects. The study was supported by the Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome (HLHS) and an NIH Grant to the Wisconsin National Primate Research Center.

The research, published in Cell Transplantation, shows that heart muscle cells derived from human induced pluripotent stem cells can safely integrate into the hearts of monkeys with right ventricular pressure overload.

Key findings of the study include:

• Successful integration of transplanted cells into the host myocardium
• Feasibility and safety demonstrated in a nonhuman primate model
• Potential to delay or prevent the need for heart transplants in patients with congenital heart defects

The research focused on right ventricular dysfunction, a condition that often affects children with congenital heart defects and can lead to heart failure. Current treatments, including surgical repair, are often temporary solutions, with many patients eventually requiring heart transplants.

Dr. Jodi Scholz, the study’s lead author, emphasized the critical need for alternative treatments, stating, “Stem cell treatments could someday delay or even prevent the need for heart transplants.”

While the study showed promising results, the researchers noted some instances of ventricular tachycardia in the animal subjects. However, these episodes resolved within 19 days.

This research represents a significant step towards clinical applications for congenital heart defects. The use of macaques in this study has been crucial in advancing stem cell therapies for various diseases, including heart disease, kidney disease, Parkinson’s disease, and eye diseases.

As heart disease remains the leading cause of death in the United States, this innovative approach to regenerating heart tissue offers hope for stronger, longer-lasting hearts across all age groups.

After 14 years at the helm of the Wisconsin National Primate Research Center (WNPRC), Dr. Jon Levine stepped down as Director on December 31, 2024, but continues his impactful neuroscience research at the University of Wisconsin–Madison and the WNPRC. Dr. Levine, a professor of neuroscience, is renowned for his studies on reproductive endocrinology and hormone actions in the brain. 

Dr. Levine’s Key Achievements 

• Expanded WNPRC’s research focus, emphasizing collaboration across fields like neuroscience, reproductive medicine, and infectious diseases. 

• Created scientific working groups that spurred innovation, collaboration, and increased grant success. 

• Led development of the WNPRC Scientific Protocol and Implementation Unit (SPI), driving research on HIV, COVID-19, Parkinson’s, and more. 

• Mentored over 15 post-docs, 30 graduate students, and numerous undergraduates, fostering the next generation of scientists. 

Looking to the future, Dr. Levine is excited about ongoing projects, particularly his research on polycystic ovary syndrome (PCOS), where he and collaborator Dr. David Abbott are studying a subset of rhesus monkeys that naturally develop the disorder. Their work could lead to deeper insights into the genetic and metabolic causes of PCOS, a condition affecting many women worldwide. 

As Levine transitions from his role as director, he remains committed to mentoring the next generation of scientists, with a particular focus on helping junior investigators launch their careers. His legacy includes not only expanded research at WNPRC but also a lasting impact on scientific collaboration and mentoring across the globe.  

Dr. Saverio “Buddy” Capuano, DVM, Associate Director of Animal Services, serves as the interim director while the center continues its mission to advance human health through innovative research. 

To learn more about Dr. Levine and his work as Director at Wisconsin NPRC, click HERE.  

In a groundbreaking leap towards a new Parkinson’s disease treatment, a stem cell therapy company has initiated a clinical trial involving human patients following the success of a novel therapeutic delivery method in non-human primates at the Wisconsin National Primate Research Center. This advance could revolutionize how we treat Parkinson’s disease. 

What is Parkinson’s? 

Parkinson’s disease is characterized as a condition that progressively impairs movement due to the loss of dopamine-producing neurons in the brain. Dopamine is a neurotransmitter crucial for coordinating movement. This leads to symptoms such as rigidity, slowness and tremors. While medications like L-DOPA can temporarily alleviate these symptoms, the drugs often lose effectiveness over time and can cause complications. 

A New Approach with Monkeys  

Researchers at the Wisconsin National Primate Research Center at the University of Wisconsin–Madison have successfully grafted dopaminergic neuronal progenitor cells into the brains of cynomolgus macaque monkeys. These cells, provided by Aspen Neuroscience, were grown from human induced pluripotent stem cells, or iPS cells. The process involved precise surgical techniques guided by intraoperative MRI, allowing for targeted delivery of the cells to areas of the brain most affected by the disease. 

The Human Connection 

The promising results in monkeys paved the way for human trials. The research highlighted the potential of using a patient’s own iPS cells to avoid immune rejection, a significant hurdle in cell therapy. This method not only aims to replace  

lost neurons but also to enhance the patients’ quality of life by reducing symptoms of depression and anxiety associated with Parkinson’s. 

Bridging the Gap to Human Trials 

The transition from animal models to human trials required meticulous planning and collaboration. The study tested different angles for cell delivery to minimize surgical risks and improve recovery times. The findings were crucial in obtaining approval from the FDA to start human trials, marking a significant step forward in the quest to find safe and effective treatments for Parkinson’s. 

Hope for the Future 

As the first human trials commence, this research not only represents a scientific breakthrough but also a sign of hope for improving the lives of millions suffering from Parkinson’s. The journey from lab to clinic underscores the power of innovative science and collaboration in tackling complex health challenges. 

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.  

When it comes to kidney transplants, compatibility between the donor and recipient is a critical factor for success. However, even when a donor and recipient are closely matched, long-term drug therapy is often necessary to suppress the recipient’s immune system and prevent the rejection of the transplanted organ. But what if there was a way to increase compatibility, reducing the need for lifelong anti-rejection medications? 

Researchers at the University of Wisconsin–Madison and Stanford University developed a groundbreaking approach that may revolutionize kidney transplants, allowing for greater compatibility between donors and recipients and potentially eliminating the need for immunosuppressant drugs. This method, tested in a nonhuman primate model, creates a dual immune system with the recipient and offers hope to kidney transplant patients, even when they are less closely matched to their donors. 

The Journey to Compatibility 

Led by Dixon Kaufman, a Professor of Surgery at UW–Madison and Director of the UW Health Transplant Center, the research team aimed to maintain kidney function without rejection in a monkey model that closely resembled human transplants. They also sought to prevent graft-versus-host disease, a complication when the donor’s immune cells attack the new host. 

According to the recent study published in Transplant International, the team worked with 11 monkeys from the Wisconsin National Primate Research Center. These monkeys had less tissue type matching than what had previously been attempted in human donor-recipient pairs. 

The major histocompatibility antigens, two key strings of tissue typing proteins found on the surface of cells, play a pivotal role in the immune system’s ability to recognize “self” and “non-self.” The monkeys in this tolerance induction study had just one match among these key protein strings, while successful human transplant pairings previously required two matches. 

The Innovative Procedure 

After receiving donor kidneys, the monkeys underwent a procedure involving thin beams of radiation, targeting key parts of their immune systems, temporarily suppressing them, and an infusion of blood and immune cells from their kidney donors. The goal was to create a mixed chimeric state in the recipients, where their immune system was a combination of two animals: part donor and part recipient.  

All animals in the study were gradually weaned off immunosuppressant drugs, and two monkeys maintained chimeric immune systems. These two animals remained healthy with normal kidney function for more than four years without experiencing rejection or graft-versus-host disease or needing drugs to suppress their immune systems. 

Dixon Kaufman noted, “This is the longest duration of tolerance induction reported in this kind of animal model. Although more challenging compared to identically matched pairs, this protocol shows it is feasible to achieve long-term tolerance between more distantly related pairs with tissue incompatibility.” 

A Brighter Future for Transplants 

Kaufman believes the knowledge gained through this research could have far-reaching implications for various donor transplants, including those from deceased donors who may be even more distantly related. As advancements continue, the hope for improved compatibility between donors and recipients becomes increasingly promising. 

A team of researchers recently delved into lower urinary tract (LUT) dysfunction, a common issue among older adults that brings challenges like incontinence, urinary infections, and reliance on catheters. These struggles often lead to a loss of independence and a need for extended care. But what causes this problem?

Researchers at the California and Wisconsin National Primate Research Centers alongside researchers from the Icahn School of Medicine at Mount Sinai set out to uncover the secrets behind LUT dysfunction, focusing on adult and aged female rhesus monkeys, giving them insights into how the issue develops in humans.

They discovered a connection between detrusor underactivity (DU), which affects bladder muscle tone, and specific metabolic markers. These markers act like clues that help researchers understand the bigger picture.

The bladder’s functioning relies on smooth muscle fibers arranged in a pattern known as the detrusor muscle. This unique structure allows the bladder to stretch and contract effectively.

Researchers also noticed patterns among the aged subjects. These subjects exhibited markers commonly associated with metabolic syndrome, such as changes in weight, triglyceride levels, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and high-sensitivity C-reactive protein (hsCRP). Interestingly, some markers, like Aspartate aminotransferase (AST), remained unchanged, while the AST/ALT ratio took an unexpected turn.

This means there is a link between detrusor underactivity and metabolic syndrome in older female primates. Factors like prior pregnancies and menopause didn’t sway the results, making this connection even more intriguing.

Dr. Ricki Colman, an associate professor of cell and regenerative biology at the University of Wisconsin–Madison and one of the study’s authors, emphasized the practical significance of their findings: “Our findings provide insights into possible mechanisms for age-associated detrusor underactivity and may guide new strategies to prevent and treat LUT dysfunction in older adults.”

As this chapter in the research unfolds, it’s clear that the relationship between LUT dysfunction and metabolism holds promise for shedding light on a common issue and uncovering new ways to address it.

National Primate Research Centers Prioritize Openness for Scientific Progress

At the forefront of biomedical and behavioral research are the seven National Primate Research Centers (NPRCs). They form a vital network dedicated to conducting and enabling groundbreaking research to improve human and animal health. Studies at the centers include development & aging, genetics & genomics, infectious disease, neuroscience & brain disorders, and reproduction & endocrinology. The NPRCs have been instrumental in driving discoveries crucial for overcoming health challenges and in helping the public understand the significance of research that involves animals.   

A Comprehensive Approach  

A priority of the NPRCs is to share information via local, regional and national outreach. Through a multifaceted approach, the NPRCs foster education and dialogue, ensuring openness about their research and the expert care of animals involved in NPRC research studies.   

From participating in local events to leveraging digital platforms, the NPRCs employ diverse strategies to make connections. NPRC.org provides the latest information for the public, and NPRCresearch.org, which is undergoing updates, ensures the scientific community has comprehensive information about the resources the NPRCs offer NIH-funded researchers. Through timely and engaging content, the NPRCs strive to explain the highly regulated research process and showcase their contributions to scientific progress.   

A Legacy of Excellence  

With a history spanning more than six decades, the NPRCs stand as pillars of scientific expertise and exemplars of public outreach. The U.S. Animal Research Openness initiative (USARO) recently featured information about the NPRCs’ outreach programs on the USARO website. This article provides encouragement for other research centers to follow the NPRC lead.   

A Future Filled with Accurate Information  

As the NPRCs continue to make scientific discoveries, their dedication to openness will continue to expand. The NPRCs believe openness helps empower individuals to make informed decisions, is critical to instilling confidence in scientific research and care of research animals, inspires future generations of scientists and ensures the public has accurate information about how research with animals is improving lives.