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.”

According to the CDC, there are currently 83,949,036 cases of Covid-19 reported in the United States. We all know someone who has been through Covid-19. Headaches, runny nose, congestion, and losing the ability to taste food are common symptoms. But, until now, there have remained many questions surrounding how COVID-19 affects the central nervous system—especially in patients who haven’t experienced a lot of respiratory symptoms. 

While damage to the central nervous system is increasingly evident, the origin remains unclear. Understanding the effects will ultimately help discover and implement future treatments.

Recently, researchers at Tulane University evaluated the neuropathology damage associated with SARS-CoV-2 infection in a nonhuman primate. As it turns out, severe brain inflammation and injury consistent with reduced blood flow or oxygen to the brain, including neuron damage, death, and more, are consistent markers, especially with primates who had little to no respiratory issues. These findings are also compatible with ones reported on autopsied human brains who died from a SARS-CoV-2 infection.

Dr. Tracy Fischer, lead investigator and associate professor of microbiology and immunology at the Tulane National Primate Research Center, states, “Because the subjects didn’t experience significant respiratory symptoms, no one expected them to have the severity of disease that we found in the brain. But the findings were distinct and profound, and undeniably a result of the infection.”

HIV (human immunodeficiency virus) attacks the body’s immune system and, if not treated, can lead to AIDS (acquired immunodeficiency syndrome).

Because of medical advancements, including antiretroviral therapy (ART), many people now live long lives with HIV, but researchers believe long-term viral control in the absence of ART (i.e. remission) might be possible. 

In pursuit of an HIV remission, researchers at the Emory National Primate Research Center (EPC) are working to lower HIV persistence. They recently discovered the anti-inflammatory protein, interleukin-10, may be responsible for helping sustain cellular reservoirs, which enable the virus to hide. This breakthrough may lead to treatments that can block the effects of interleukin-10 and, therefore, reduce viral persistence, which is critical to finding alternative therapies to control HIV. 

The team worked with rhesus macaques infected with simian immunodeficiency virus (SIV), the animal form of HIV, to determine how interleukin-10 regulates the survival of cells known to harbor HIV. The team also studied the effects of blocking this protein to determine if doing so would reduce the persistence of the virus when used in combination with ART.

Mirko Paiardini, PhD, senior author of the study, said when his research team looked at lymph node tissues, they found the vast majority of cells infected with SIV were within close proximity to cells expressing interleukin-10. This was the case in both chronically infected animals and in those treated with ART.

The team found in the monkeys treated with ART and an antibody against interleukin-10 a significant reduction in the frequency of immune cells harboring SIV in the macaques’ lymph nodes. The discovery confirms Interleukin-10 signaling is critically involved in promoting the survival of the cells harboring the virus and warrants further research in nonhuman primates.

Human immunodeficiency virus (HIV) attacks the body’s immune system, resulting in rashes, fevers, fatigue, swollen lymph nodes, and other symptoms. It affects over 37 million people globally. When left untreated, HIV infections can progress to acquired immunodeficiency syndrome (AIDS), leading to a damaged immune system, severe opportunistic infections, and death.

Most replicating HIV – and its monkey version, simian immunodeficiency virus (SIV) – is found in follicles of the lymphoid tissues. However, most cytotoxic T-lymphocytes, the cells clearing HIV from the body, cannot reach the follicles. This explains the need for lifelong use of antiretroviral therapy’s current standard treatment. However, only 57% of those living with HIV are undergoing antiretroviral therapy, which leaves the rest able to infect others with the virus. Therefore, there is an urgent need for new treatment options, especially for those who do not have lifelong access to healthcare.

A group of AIDS researchers working with immunology and animal care experts on rhesus monkeys at the Wisconsin National Primate Center investigated the possibility of a new therapy targeting virus-specific T-cells to the follicles. They did so by engineering therapeutic T-cells to enter and concentrate in the lymphoid follicles to reduce viral replication. Led by Pamela Skinner, professor of veterinary and biomedical sciences at the University of Minnesota, the team used T-cells to express a chimeric antigen receptor (CAR) targeting the SIV virus. They added a follicular homing receptor called CXCR5 so the CAR/CXCR5 T-lymphocytes could kill the infected cells in the lymphoid follicles. The homing receptor allowed the T-cells to migrate into the follicles, which previously limited the effectiveness of the body’s response to infection.

In six SIV-infected rhesus monkeys, the CAR/CXCR5 T-cells were able to migrate to the follicles within two days and directly interact with the virally infected cells. Fluorescent imaging allowed the researchers to discover these T-cells could replicate and increase within the follicles. Even though levels of the specialized T-cells declined within four weeks after administration, the treated primates were able to maintain lower concentrations of SIV in their blood and follicles than those not given the CAR/CXCR5 T-cell immunotherapy. The researchers and veterinarians also looked at possible side effects of this treatment and found none of the primates had a poor reaction to T-cell administration.

The study, published in Public Library of Science Pathogens, provided preliminary evidence for effective and safe treatment of engineered T-cells for HIV infection. Data from these researchers set the stage for future preclinical studies involving larger populations of non-human primates to confirm the effectiveness of this treatment, along with studies looking at combining this treatment with other therapies.

Zika is spread mainly through the bite of an infected Aedes species mosquito. And while many people infected with the Zika virus will only have mild symptoms, contracting Zika during pregnancy can lead to severe brain defects.  

 The 2015-2016 Zika outbreak in Brazil and other countries in the Americas caused a surge in miscarriages and a constellation of congenital disabilities, prompting the World Health Organization to declare a public health emergency of international concern. 

 While there has never been a vaccine or medicine to prevent Zika, a recent collaboration between Trudeau Institute, Texas Biomedical Research Institute’s Southwest National Primate Research Center (SNPRC), and Walter Reed Army Institute of Research (WRAIR) demonstrated a vaccine candidate successfully prevented the virus from passing from mother to fetus during animal studies. 

 In-Jeong Kim, Ph.D., a viral immunologist at Trudeau Institute and the first paper author states, “Our proof-of-concept studies conducted at Trudeau and Texas Biomed show very promising results that the vaccine given before pregnancy will provide high levels of protection for mothers and babies.” 

 Testing pregnant women is highly restrictive due to ethical and safety reasons, which is why the Trudeau Institute and Texas Biomed team evaluated the vaccine in pregnant mice and marmosets. The results? More than 90% effectiveness in marmosets, making it a viable approach for countering the persistent threat of Zika in humans.