Texas Biomed and SNPRC featured in Texas Monthly

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Story highlights the national research primate shortage and balances concerns around animals in biomedical research with the global need to develop vaccines and cures that help both animals and people.

Blake Harrington looking at baboons
Blake Harrington looks out over the nearly 6-acre baboon corral at Southwest National Primate Research Center at Texas Biomed.

Texas Biomed is featured in a Texas Monthly story that details how our infectious disease research enabled the fastest development of a vaccine in history, which helped slow a raging pandemic and save countless lives. The magazine piece highlights the strategic growth of the Institute, its vision for the future and the role of its Southwest National Primate Research Center (SNPRC).

Reporter Will Bostwick wrote: for each animal used in COVID research…, “countless more human lives were saved. Infectious disease experts worldwide agree that there will be other pandemics, and Texas Biomed intends to help develop the next cures.”

The story goes on to lay out a fundamental crux of biomedical research: to develop cures and vaccines, nonhuman primates are a required and important part of the process. Not only because the Food and Drug Administration requires that most treatments be tested in animals before being given to humans, but also because the technologies that one day aim to replace animals in research are not advanced enough to adequately replicate a complete biological system.

In the article, Texas Biomed’s President/CEO Larry Schlesinger and SNPRC Director Corinna Ross share how deeply committed Texas Biomed and SNPRC are providing the absolute best care to its animals. Dr. Schlesinger spoke about the Institute’s work to address the current national shortage of research primates by expanding animal housing and research space.

Here are a few excerpts from the story:

Thomas Slick Jr., an eccentric 26-year-old heir to an oil fortune, founded what became Texas Biomed on a working cattle ranch eight miles west of downtown San Antonio, in 1941. Much of its early work was devoted to livestock breeding, including the creation of a popular Brangus hybrid that combined the virtues of Brahman and Angus cattle. Slick later became a world traveler who led expeditions in search of the yeti in the Himalayas and Sasquatch in the Pacific Northwest.

In the fifties, the institute turned its attention to biomedical research and began importing baboons from Africa. By the eighties, it was testing early treatments for HIV and hepatitis C. In 1999 it established the Southwest National Primate Research Center, one of only seven such facilities in the country funded by the National Institutes of Health and the only one not associated with a university. Today it’s home to roughly five hundred marmosets, one thousand baboons (the world’s largest colony), and 1,500 macaques.

When the COVID-19 pandemic began, China, the United States’ top source for nonhuman primates, decided to begin keeping its supply to itself. This led to a bottleneck in animal-research projects elsewhere in the world. Cambodia, the next top supplier, partially filled the gap, but in November 2022 it, too, halted exports, out of concerns that it was contributing to the poaching of endangered wild macaques. Experts say the primate shortage has compromised critical biomedical research in the U.S., and Texas Biomed’s leaders have determined that the institute should help bolster the domestic supply.

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Much as Houston’s MD Anderson is known as the premier cancer center in the U.S., Texas Biomed aspires to be the premier infectious disease institute. “In Texas we’re not known enough,” Schlesinger says. “I don’t think people appreciate just how much power we have in science.” In addition to its work on Pfizer’s COVID-19 vaccine, Texas Biomed was involved in developing Regeneron Pharmaceuticals’ monoclonal antibody therapy, as well as in major advances for hepatitis C patients that led to a 2020 Nobel Prize for some of its collaborators. Ebola therapies and vaccines tested in the institute’s Biosafety Level 4 lab have also shown promise. And last year the NIH selected the institute as a training center for tuberculosis researchers.

None of this would be possible without its nonhuman primates, Schlesinger insists. 

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“We’re at the cutting edge of science that will enable us to replace monkeys someday,” Schlesinger agrees. “We want that more than anyone. Animals are very expensive, labor intensive, and require a lot of care.” But Schlesinger pushes back against those who say animal testing should be supplanted immediately by the new options. “The reality is it’s not ready for prime time,” he says of the emerging technology. 

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Though the Food and Drug Administration has signaled that it will accept alternatives to animal testing in some cases, a congressionally mandated report published this year by the National Academies of Science, Engineering, and Medicine found that none of the alternatives can fully replace nonhuman-primate testing—at least not yet.

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“I’m thinking about solving the world’s problems,” he (Schlesinger) says. “The goal is to use less animals, to use them in a more sophisticated fashion whenever possible, and to make sure that the studies are validated, so that the work done actually moves forward in the proper fashion. That’s what we can do. And that’s what I think Texas Biomed does really well.”

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A Pfizer senior director would later say this swift action by the institute put the pharmaceutical giant a month ahead in getting its vaccine to the public. For each of the dozens of animals sacrificed, it could be argued, countless more human lives were saved. Infectious disease experts worldwide agree that there will be other pandemics, and Texas Biomed intends to help develop the next cures. 

Read the full article here.

NIH continues investment in SNPRC’s macaque colony dedicated to HIV/AIDS research

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SAN ANTONIO (May 31, 2023) — Texas Biomed’s Southwest National Primate Research Center announced today the renewal of a $10 million National Institutes of Health (NIH) grant to support a rhesus macaque colony dedicated to HIV/AIDS research.

The U42 grant, which is spread over four years, will support the ongoing care and growth of the HIV/AIDS research colony from 800 to 1,000 animals.

“This colony has been with SNPRC since 2000 and has played crucial roles in supporting hundreds of studies into HIV/AIDS mechanisms, treatments and vaccines,” says current SNPRC Director Corinna Ross, PhD. “We are grateful for NIH’s continued support of this valuable resource. This grant will help us strategically grow the colony to help meet the needs of AIDS researchers nationwide, which is especially important as we face an acute shortage of nonhuman primates for biomedical research.”

The macaques in this colony are especially important for HIV/AIDS research for several reasons: they are free from specific pathogens, such as herpes B virus and simian immunodeficiency virus (SIV), the monkey equivalent of HIV; they have extremely well-documented genetics and are carefully bred to maximize genetic diversity. This all helps make them robust models for studying complex, full-body responses to a potential vaccine or therapy.

While as much research as possible is done in cells and small animal models, before a treatment or vaccine can be given to people, its safety and efficacy must be evaluated in nonhuman primates. Every study is scrutinized to ensure as few animals are used as possible, while still providing enough data to draw important conclusions.

The U.S. already faced a shortfall of nonhuman primates for research prior to the COVID-19 pandemic. The pandemic made things worse as many animals were needed to help evaluate COVID mechanisms, treatments and vaccines. Additionally, China stopped exporting nonhuman primates during the pandemic, cutting off one of the main sources of research animals.

The National Academies of Science, Engineering and Medicine released a report on the current status and future needs of nonhuman primates in biomedical research in May, following a year-long review.

“The report says the U.S. needs to prioritize expansion of domestic nonhuman primate breeding programs. Relying on importing these animals from other countries is unsustainable, and dependence on international sources undermines the security of the nation’s biomedical research enterprise,” a National Academies press release states.

SNPRC is one of seven National Primate Research Centers dedicated to managing breeding colonies and nonhuman primate research for the nation. SNPRC hosts several different nonhuman primate species, including baboons, macaques and marmosets, which support research in a wide variety of diseases in addition to HIV/AIDS, including diabetes, obesity, cancer, hepatitis, tuberculosis and COVID-19. Texas Biomed is in the process of building a new Animal Care Complex, which will help SNPRC expand its colonies.

“Our team of more than 150 caretakers, behavioralists, veterinarians and technicians are committed to providing the very best care and life for our animals,” Dr. Ross says. “We are proud to help address the need for nonhuman primates in research, but know additional investment will be required if we are to meaningfully overcome the shortage identified by the National Academies.”

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Funding Acknowledgements: This release describes funding provided by the The Office of the Director, National Institutes of Health under award number U42OD010442. The Office of the Director, National Institutes of Health also provides core funding for SNPRC under award number P51OD011133.

FOCUS: National Primate Research Centers turn 60

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Southwest National Primate Research Center is proud to be part of the success of the national network established in the 1960s.

The National Primate Research Centers (NPRCs), which are committed to helping people live longer, healthier lives through nonhuman primate research, are celebrating six decades of support from Congress and the National Institutes of Health in 2022.

The Southwest National Primate Research Center (SNPRC) at Texas Biomed is the youngest of the seven NPRCs. SNPRC was officially established in 1999 to help support biomedical research across the nation with its breeding colonies. Texas Biomed was well positioned to join the network, having housed a variety of primate species for scientific research since the 1950s.

Deepak Kaushal, PhD, oversees the SNPRC $20+ million-a-year operation, which encompasses about 2,500 primates and 150 staff dedicated to animal health and welfare. He works closely with the NPRC network, synergizing resources and coordinating research.

“Having overlapping but varied areas of expertise, we are able to cover a larger gamut of human diseases and conditions, while being mindful not to waste precious resources,” Dr. Kaushal says.

SNPRC is unique among NPRCs. It the only one hosted by a nonprofit research institute, not a university. It is the only NPRC with a biocontainment safety level 4 lab on campus. It is also the only center with three different breeding colonies: Indian rhesus macaques, African baboons and New World marmosets.

Macaques are proven models for infectious disease research. Baboons make good models for metabolic studies in areas like diabetes. Marmosets are useful for studying aging and neurodegenerative diseases such as Alzheimer’s and Parkinson’s.

“Our focus has been more diversified in species than other centers,” explains Corinna Ross, PhD, who is SNPRC’s Associate Director of Research and colony administrator. “We have the same goal and mission, though, to serve as a resource for nonhuman primates for translational work.”

While many people dream of a future where Artificial Intelligence and organs-on-a-chip can solve health crises, animal models are the best-available example of how an entire body will react to a vaccine or treatment. As our closest relatives, nonhuman primates also help researchers learn crucial details about the earliest stages of diseases, which can unlock new interventions.

“Some people are under the impression that we should be able to only conduct studies in petri dishes or on the computer,” Dr. Ross says. “We are not at that point yet.”

The primates at SNPRC have made significant contributions to human health.

“People might be surprised to know these monkeys helped test the COVID vaccines that have gone into the arms of millions of people around the world,” Dr. Kaushal says. “They have also been instrumental in breakthroughs in artificial reproduction and lung treatments for premature infants.”

With so many global health challenges — diabetes, drug-resistant bacteria, the next pandemic virus — the NPRCs and nonhuman primates will continue to play a central role in finding vaccines, treatments and cures in the decades to come.

This story appeared in the Summer 2022 edition of TxBiomed magazine. See more stories from TxBiomed here.

FOCUS: SNPRC’s Commitment to Care

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The Southwest National Primate Research Center (SNPRC) is committed to not just meeting, but exceeding, the highest standards of research animal care. Recent inspections from federal regulators and external reviewers found that SNPRC has once again passed its checks with flying colors.

Earlier this year, the U.S. Department of Agriculture came for one of its unannounced visits. Officials inspected facilities, checked on animals and reviewed scientific protocols to see if all federal Animal Welfare Act regulations are being followed.

“We do our absolute best to care for the animals,” says Attending Veterinarian Diana Scorpio, DVM, MPH. “When you get a clean report from USDA like we did this spring, we feel such great pride in our animal care program.”

This follows last fall’s review by AAALAC International, which is a nonprofit organization promoting the humane treatment of animals in science. AAALAC renewed SNPRC’s full accreditation status for three years.

“Being accredited means we are adhering to the highest standards — and in some cases, exceeding the standards — for use and care of research animals,” Dr. Scorpio says. “AAALAC looks at everything related to animal care, from housing to breeding to the enrollment of nonhuman primates in studies.”

This external validation underscores SNPRC’s efforts to go above and beyond caring for its animals, which are a precious resource. Global companies and research organizations like the National Institutes of Health are also more likely to partner with SNPRC.

“A lot of organizations use the accreditation and inspections to decide who they want to work with,” says Dr. Scorpio, who is also a Professor and Associate Director of Veterinary Resources and Research Support. “If you don’t have those, you don’t have trust.”

SNPRC provides creature comforts the nonhuman primates need. The macaques, baboons, marmosets and chimpanzees have plenty of shade, shelter, food and around-the-clock medical care. They have indoor-outdoor housing and are intentionally placed in species-appropriate social groups or pairs. A trained team of experts in primate biology and behavior design species-specific enrichment activities to ensure the animals are engaged and displaying typical behaviors.

“My philosophy is that we are advocates for the nonhuman primates to make sure we are doing right by them and by the science,” Dr. Scorpio says. “They are providing us with information that directly helps the global good.”

If there ever came a point when animal research is no longer necessary, Dr. Scorpio says that would be welcome. In the meantime, animal models remain the gold standard for capturing critical aspects of living physiology and are vital for discovering biomedical breakthroughs.

“As veterinarians, respect for animal life is part and parcel of our profession,” Dr. Scorpio says. “These animals are a privilege to work with. They deserve to have the best of the best. We want to ensure they are given the highest level of care.”

This story appeared in the Summer 2022 edition of TxBiomed magazine. See more stories from TxBiomed here.

Starting antiretroviral therapy early essential to battling not one, but two killers

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Medication against the nonhuman primate version of HIV given two weeks after infection helped keep tuberculosis in check.

SAN ANTONIO (February 15, 2022) – Two weeks makes a big difference in treating the animal version of HIV and latent tuberculosis, researchers from Texas Biomedical Research Institute, Southwest National Primate Research Center and colleagues report this month in the Journal of Clinical Investigation. The finding is another piece in the puzzle of the complex interaction between HIV and tuberculosis (TB), and can help advance development of therapies and a combined vaccine for the two diseases in humans.

“Most humans are able to control a low dose of TB infection by maintaining it in a dormant form called latent tuberculosis infection,” says Riti Sharan, PhD, a staff scientist at Texas Biomed and first paper author. “But if they get co-infected with HIV, then there is a high possibility that TB is reactivated and the patient ultimately dies of TB. Our objective is to improve existing interventions or identify new ones to prevent latent TB from being reactivated.”

To help study what happens in humans, researchers turn to nonhuman primates, which contract simian immunodeficiency virus (SIV), the monkey version of HIV, as well as tuberculosis. The researchers found that when animals with a latent TB infection start combined antiretroviral therapy (cART) against SIV two weeks after infection, the animals fare much better than if cART is started at four weeks post SIV infection.

“Originally, we did not think that two weeks would make this much of a difference, but to our surprise, it did,” Sharan says. “The findings were very dramatic and clear.”

Specifically, in the group that started cART at two weeks post infection, chronic immune activation was significantly reduced, as was SIV replication, and latent TB was not reactivated as much as in the group that started cART four weeks post infection. In fact, the lungs in the group that started treatment at four weeks looked more like they were not receiving any treatment at all.

Lung tissue of animals with TB
Lung tissue of animals with TB that started cART two weeks post SIV infection (left) versus at four weeks post SIV infection (right). There are far fewer green spots on the left, which indicate fewer macrophages are dying and latent TB is kept more under control, thanks to starting cART earlier. Red spots are also macrophages. Credit: Texas Biomed

Chronic, or ongoing, activation of an immune response, might sound like it should be a good thing to help fight illness. But it can also play a central role in exacerbating illness. When the immune cells are chronically activated, it leads to exhaustion and cell death, and this opens up a major gap in the body’s defense system, Sharan explains. That is when is appears latent tuberculosis can become reactivated.

“This paper adds to the growing body of evidence from our lab that shows chronic immune activation is key to driving reactivation of latent TB,” says Deepak Kaushal, PhD, a professor at Texas Biomed and senior paper author. “But it is the first to really look at the timing difference for administering ART in animal models, which is will be critical for future studies and helping develop treatments and vaccines.”

The researchers note that the difference of two weeks may not directly apply to humans, in part, because most people are unlikely to be diagnosed and begin treatment for HIV within two weeks of infection. The real value of the finding is identifying chronic immune activation as the main driver of latent TB reactivation following HIV infection, and now being able to study potential mechanisms for protection.

“Ultimately, we aim to use this information to design a therapy that would enable patients to prevent latent TB reactivation by limiting the HIV-driven chronic immune activation,” Sharan says.

The research was done in collaboration with the Emory University School of Medicine, Tulane National Primate Research Center and Washington University in St. Louis.

This investigation used resources supported by the Southwest National Primate Research Center grant P51 OD011133 from the National Institutes of Health Office of Research Infrastructure Programs.

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ABOUT TEXAS BIOMED

Texas Biomed is one of the world’s leading independent biomedical research institutions dedicated to eradicating infection and advancing health worldwide through innovative biomedical research. Texas Biomed partners with researchers and institutions around the world to develop vaccines and therapeutics against viral pathogens causing AIDS, hepatitis, hemorrhagic fever, tuberculosis and parasitic diseases responsible for malaria and schistosomiasis disease. The Institute has programs in host-pathogen interactions, disease intervention and prevention, and population health to understand the links between infectious diseases and other diseases such as aging, cardiovascular disease, diabetes and obesity. For more information on Texas Biomed, go to www.TxBiomed.org.

Initial COVID-19 infection on the single-cell level, revealed

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Sequencing more than 170,000 single cells from animal models have provided exceptionally detailed insight into the early immune response to SARS-CoV-2 in the lungs. The findings will help inform future treatment options for the current pandemic and future coronaviruses.  

Using fluorescent markers, Texas Biomed researchers and colleagues identified the cell populations active in the lung in the first few days of COVID-19 infection. Under the microscope, they observed immune cells called macrophages (the large multicolored circles) responding to SARS-CoV-2 infection, at three days following infection (center). These macrophages were not present in the lung before infection (left) and most were no longer detected two weeks after infection (right). Blue spots are nuclei of normal lung cells. Credit: Texas Biomed

SAN ANTONIO (February 7, 2022) – What is going on at the single-cell level in the first days of SARS-CoV-2 infection in the lungs?

Researchers at Texas Biomedical Research Institute and Southwest National Primate Research Center (SNPRC), in collaboration with Washington University in St. Louis, have clarified what immune cells are present in the lungs in the first days of SARS-CoV-2 infection, and what some of those cells are doing to fight off the virus. The findings, reported in Nature Communications this week, will help guide the development of future treatments for COVID-19.

“This is the most detailed analysis of early SARS-CoV-2 infection to date thanks to the latest single-cell sequencing technologies, and animal models developed at Texas Biomed and SNPRC,” says Deepak Kaushal, Ph.D., SNPRC Director and senior paper author.

The analysis has shed light on a key mystery throughout the COVID-19 pandemic: the role of a class of signaling proteins called Type I Interferons (IFN). During viral infections, interferon molecules act like sentries or alarm bells blaring “intruder alert!” to other cells, so they can boost their defense systems. However, some reports have shown a lower Type I Interferon response to SARS-CoV-2, allowing the virus to spread more readily. At the same time, runaway interferon “cytokine storms” have been a hallmark of severe COVID-19.

Scientists have been trying to figure out if interferon fights SARS-CoV-2 or is somehow dysregulated, especially early on in infection. Clarifying this is important for developing treatments that aim to limit harmful inflammation linked to excessive interferon activity, without blocking its protective mechanisms.

This new research shows interferon plays a key role in clearing the virus, by alerting other immune cells, called macrophages, to search and destroy the virus. Macrophages are akin to Pac-Man, gobbling up cells infected with the virus.

“Our analysis shows there is a massive population of macrophages in the lungs at day three after infection, amounting to 80 to 90 percent of all cells in the airways at that moment,” says Dhiraj K. Singh, Ph.D., a Staff Scientist at Texas Biomed and first paper author. “We can also tell by looking at the genes that are activated in those macrophages, that they are specifically responding to an interferon signal.”

The finding was possible thanks to the latest, highest-resolution genetic sequencing technology: single-cell RNA sequencing. The team sequenced the gene expression profiles of more than 170,000 individual cells. These profiles, which tell them what genes are turned up or down, indicate what the cell is and what it is doing at the time. Singh worked closely with Shabaana Khader, Ph.D., and Maxim Artyomov, Ph.D., and their teams at Washington University in St. Louis to analyze and interpret the massive amounts of raw, high-resolution data.

“RNA sequencing has been around for 10 years, but it averages out gene expression activity for an entire tissue,” Singh says. “In contrast, the latest single-cell RNA sequencing can tell you what genes are on and off in say, B cells versus T cells. It is so much more specific.”

single cell sequencing data
Using single-cell RNA sequencing, the researchers identified the different cell types present in the lungs before COVID-19 infection (left), in the first few days of infection (center), and towards the end of infection (right). Each color represents a different cell type. The red represents macrophages, which clearly increase at three days post infection. Credit: Texas Biomed

But the data could not have been collected in the first place without animal models. To get a snapshot of the lung environment before, during and after infection, scientists collect what amounts to a lung wash at key time points from rhesus macaques.

“Often, by the time people go to the clinic when they are sick, the virus is already well established,” Singh says. “Primates are the only model where we can actually look at those early acute responses.”

Kaushal underscored how at the start of the COVID-19 pandemic, the San Antonio community rallied behind Texas Biomed and SNPRC, donating more than $5 million in a week to support the institute’s efforts to develop animal models for COVID-19 research. The animal models have since been critical for testing vaccines and therapies, including the Pfizer-BioNTech vaccine and Regeneron’s monoclonal antibody cocktail.

“This new research is a continuation of the animal model that we generated, which would not have been possible without the generous contribution of the San Antonio community and ongoing support from the National Institutes of Health’s Office of Research Infrastructure Programs,” Kaushal says. “It shows once you’ve established a model, what is possible. You can really advance knowledge in the area.”

Singh has recently received a San Antonio Medical Foundation grant to see what happens when more interferon is added to the lungs, and compare that with other ongoing studies blocking interferon. If the studies ultimately confirm interferon’s positive role in marshalling macrophages early in infection, it could potentially lead to interferon-based therapies for COVID-19. These have been tried for other diseases, and so could move quickly to clinical trials.

“In my opinion, the potential applications don’t stop at COVID-19,” Kaushal says. “It’s quite likely that the next pandemic in the next 10 years or so will be caused by another coronavirus. So having all this knowledge is going to be very critical.”

This investigation used resources that were supported by the Southwest National Primate Research Center grant P51 OD011133 from the Office of Research Infrastructure Programs, National Institutes of Health.

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ABOUT TEXAS BIOMED

Texas Biomed is one of the world’s leading independent biomedical research institutions dedicated to eradicating infection and advancing health worldwide through innovative biomedical research. Texas Biomed partners with researchers and institutions around the world to develop vaccines and therapeutics against viral pathogens causing AIDS, hepatitis, hemorrhagic fever, tuberculosis and parasitic diseases responsible for malaria and schistosomiasis disease. The Institute has programs in host-pathogen interactions, disease intervention and prevention, and population health to understand the links between infectious diseases and other diseases such as aging, cardiovascular disease, diabetes and obesity. For more information on Texas Biomed, go to www.TxBiomed.org.