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New Clues to COVID in Vulnerable Patients

WaNPRC Core Scientist Megan O’Connor just published her latest research in Frontiers in Immunology exploring what happens when there are co-infections of HIV and COVID-19 in rhesus macaques. The implications are important for future Covid treatments for people with weakened immune systems.

O’Connor, who is also an Asst. Professor in the Department of Laboratory Medicine and Pathology at the University of Washington, found that monkeys with SIV (a virus similar to HIV in humans) who were co-infected with COVID-19 had COVID longer, had a weaker immune response, and underwent changes to their gut and lung microbiomes. And that these responses were different from monkeys with COVID who were otherwise healthy.

“This work is very exciting because it shows that studying monkeys can help us ask important questions and track responses that are hard to study directly with people with COVID-19,” she said.

ai-generated image depicting a monkey, a covid virus, an HIV ribbon and a broken shield.

Her study found that the COVID-19 virus stayed in the nose and throat of SIV-infected monkeys longer than it usually does in healthy monkeys. And that the SIV-infected monkeys didn’t make as many antibodies and immune cells to fight Covid-19. Their immune systems didn’t sound the alarm properly. And the mix of bacteria in the SIV-infected monkeys’ throats and gut changed temporarily during the COVID-19 infection. What’s more, the COVID-19 virus started to evolve while inside the SIV-infected monkeys.

The monkeys experienced mild COVID symptoms and their lungs didn’t show much damage.

Many of the outcomes in SIV-COVID-19 co-infected monkeys are similar to what is seen with COVID-19 in individuals that have weakened immune systems, including people living with HIV, those with cancer, and the elderly. This research may help doctors understand why people with HIV, and other people with a, might be contagious with COVID for a longer time, not respond to vaccines as well and be at higher risk for re-infection and complications.

This might help scientists create and test new vaccines and treatments specifically for people with weakened immune systems. It might also help them understand “long COVID” since some of the same problems happen in both conditions.

Dr O’Connor and her team are currently studying whether monkeys with SIV that have already fought off COVID-19 are protected against a secondary exposure to COVID-19.

Evidence of Bipartisan Support for Research in D.C.

screenshot of the livestream of the senate hearing. it depicts a dais for senators at the back of the image and a hearing room of seats before themI recently returned from Washington, D.C., where I was pleased to see something uncommon right now: bipartisan support for biomedical research. I want to applaud it and call out what WaNPRC is doing to continue to deserve that support.

I heard Republicans and Democrats alike praise the benefits of research at a Senate Appropriations Committee hearing entitled: Biomedical Research: Keeping America’s Edge in Innovation. Both the chair and vice chair, Sen. Susan Collings (R) Maine and Sen Patty Murray (D) Washington, spoke forcefully on the need for the federal government to continue funding biomedical research.

Senator Collins pointed out that every dollar of funding from the National Institutes of Health generates new economic activity of more than $2.50.  But the imperative to keep investing is “not just about scientists and researchers and economic activity,” she said.

“If clinical trials are halted, research is stopped. And laboratories are closed. Effective treatments and cures for diseases like Alzheimer’s, Type 1 Diabetes, childhood cancers, and Duchene’s Muscular dystrophy will be delayed or not discovered at all. We must preserve and strengthen America’s leadership for the sake of families all across this country,” she said.

Senator Murray concurred, pointing to the obvious benefits of government-backed research.  “Those investments have paid off in so many ways. Not just billions in economic activity, hundreds of thousands of jobs and a medical research enterprise that is the envy of the world. They’ve also paid off with genuine miracles. Cures that were once impossible, treatments that were once unthinkable. These are investments that give patients hope for the future, that give them back a live derailed by a disease, that give people precious more time with their loved ones. Which is why I am so deeply alarmed that President Trump has taken a wrecking ball to our biomedical research enterprise.”

Senator Murray was referring to attempts to gut funding by cutting indirect costs that provide the very buildings and equipment and other support that researchers need to do this work, and by attempts to slash contracts and gut agencies that fund research and protect public health.

As I sat in the chamber, I was deeply moved by the personal story of one witness at the hearing. Emily Stenson is a mom whose daughter Charlie was three when she was diagnosed with cancer. With Charlie, now five, on her lap, Ms. Stenson testified that her daughter, whose cancer is in remission, was benefiting from a new mRNA-backed test to detect relapse.  A test discovered through research at Seattle Children’s Hospital and the University of Washington.

“We first learned about this test in 2023, and knowing it’s almost within reach brings us so much hope. It’s real proof that continued research doesn’t just change lives—it saves them,” she said. Then she added, “…if you were in my shoes, you would want to know that everything possible was being done to save your child or grandchild…. Cuts to medical research are not just numbers on a spreadsheet—they are stolen chances, unfinished stories, and futures left unrealized… That is why I am asking you today: please continue to fund and prioritize pediatric medical research. Every investment you make saves lives, protects futures, and gives children like Charlie a fighting chance to grow up and thrive.”

At WaNPRC, we are deeply motivated by the impact our research has on human and animal health. Some of us are motivated by personal experience, having benefited from that research.

And while the administration vows to phase out animal testing requirements for certain treatments, I believe we can be part of a future that contributes to reaching the goal of using New Approach Methodologies (NAMs) that can reduce animal  testing. Right now, it’s not clear if NAMs can ever fully replace animal testing, but it’s becoming clearer that it can help reduce it. Examples include using Artificial Intelligence, “organs on a chip” to recreate what happens in a body’s organs, or 3D cell cultures that mimic the structure of organs. These are great ideas, but they aren’t full realized yet.  These technologies cannot replace animal models or replicate the complex biological systems such as the immune system, metabolic processes and the brain.

To help get there, we need to validate these alternative approaches and WaNPRC can and will be a party to research to prove these approaches – and others that may be discovered. To accelerate this, WaNPRC is planning to offer a NAM Ignition Award. The purpose of this award will be to focus on nonhuman primate models to support our mission in the 3Rs of animal welfare. We anticipate these projects will significantly assist the development, validation and scaling of non-animal approaches.

But it will take the continued bipartisan support and federal investment to get there. I look forward to WaNPRC contributing to that future.

WaNPRC Director Featured for Biomedical Research Awareness Day 4/17

Image depicts the topic of BRAD: Unlocking Prevention: How Vaccine Researh in Animals Saves People and Animals.  Imagine a world wihtout vaccines. No protection from Polio, no flu shots to prevent seasonal oubreaks, and no defense against emerging disease like COVID-19. Vaccines have saved millions of lives adn were made possible only through vital animal research.
This talk wiht focus on how animals, including rodents and nonhuman primates, are essential to our goal to develop new vaccines that an prevent future epidemics and pandemics caused by infectious diseases.  WaNPRC director Dr Deborah Fuller will talk about the emergence of Valley Fever a serous fungal disase that is rapidly spreading due to climate change and how one small colony of nonhuman primates in the Southwest United States may hold the key to deeloping a vaccine that can protect humans and their pets.  Join the webinar thursday, April 17, 9-10am pacific.

Unlocking Prevention: How Vaccine Researh in Animals Saves People and Animals.

WaNPRC director Dr Deborah Fuller is the featured speaker for Biomedical Research Awareness Day, an annual international outreach program by Americans for Medical Progress.

Imagine a world without vaccines. No protection from Polio, no flu shots to prevent seasonal outbreaks, and no defense against emerging disease like COVID-19. Vaccines have saved millions of lives and were made possible only through vital animal research.
This talk will focus on how animals, including rodents and nonhuman primates, are essential to our goal to develop new vaccines that an prevent future epidemics and pandemics caused by infectious diseases. Dr Fuller will talk about the emergence of Valley Fever a serous fungal disease that is rapidly spreading due to climate change and how one small colony of nonhuman primates in the Southwest United States may hold the key to developing a vaccine that can protect humans and their pets.

Join the webinar Thursday, April 17, 9-10am PT. Find out more and register here.

Dr Duran-Struuck Joins Core Faculty

A photo of a smiling Dr Raimon Duran-StruuckWaNPRC Director Dr. Deborah Fuller today welcomed Dr Raimon Duran-Struuck as a core faculty member of the Washington National Primate Research Center.  Dr Duran-Struuck is the Chair and a Professor in the UW Department of Comparative Medicine (DCM).

A passionate advocate for research animals, Dr Duran-Struuck says he’s inspired by the professionalism and care of people in research and the quality of our work with nonhuman primates. He says he’s “very excited” to contribute to advancing human and animal health.

“I’ve been working with NHPs for a long time, and I’ve always thought NHPs are an extremely valuable model to leverage our discoveries for safety and efficacy,” he said. “At end of the day what I tell my residents is that what we do here is to enhance discoveries. Think of a child w leukemia or a patient who depends on our discoveries. To me, that translates to being a small part of a big team that hopefully will be part of a big discovery.”

As an experienced lab animal veterinarian, researcher and instructor to medical students, Dr Duran-Struuck specializes in lab animal medicine and transplant immunology. He has published studies about immunotherapies for transplant rejection and Graft Versus Host Disease, which is a complication that can result from transplants of stem cells to treat blood disorders.

“I’m thrilled to welcome Raimon on board,” said Director Deborah Fuller.  “He brings a unique and highly impactful research program in transplant immunology that will further broaden the expertise of our world-renowned Gene Therapy and Regenerative Unit. As chair of DCM, Raimon also plays a crucial role in supporting all non-NHP animal research at UW and I very much value his expertise and efforts to support our common goals.”

Dr Duran-Struuck received his BS is biochemistry from Tufts University before earning his DVM there. He received his PhD in Immunology from the Universitat Autonoma de Barcelona. Prior to joining DCM, he was an Associate Professor in the Department of Pathobiology and a Director of Regulatory Affairs for University Lab Animal Resources at the University of Pennsylvania. Prior to that, he held research, clinical, and teaching positions at the Transplantation Biology Research Center at Massachusetts General Hospital, the Harvard University Department of Surgery, Tufts University, and Columbia University Medical Center.

Discoveries Drive Pandemic Preparedness and Economic Stability

Scientists and our public health infrastructure are critical for pandemic preparedness. Zika virus, a mosquito-borne disease with devastating effects on fetal brain development, continues to present a significant public health threat with far-reaching consequences for the U.S. economy and society. The virus gained global attention during the 2015-2018 epidemic, which was found to cause severe birth defects and disrupted birth rates and economies, across the Americas.

WaNPRC Associate Director of Research Kristina Adams Waldorf has been pivotal in identifying the threats posed by the Zika virus, and her findings are a perfect example of why research is essential to protect the U.S. public health and our economy. Dr Adams Waldorf’s research conclusively proved that Zika virus caused fetal brain injury, which reduced alternate theories and focused public health efforts.

Although the Zika virus epidemic began in Brazil, it wasn’t long before cases began spreading in Florida and Texas. This is why studying viruses in faraway places that can travel in the blood of an infected person and jump into mosquito populations in the U.S. is so important.

In early 2016, the news about Zika virus had reached mainstream newspapers in the U.S. Then, in the summer of 2016, the virus was found to be spreading locally in areas of Miami. Seemingly overnight, key voting populations and economic drivers in Florida were galvanized to support the scientific research for Zika virus.

“I was being contacted by real estate developers in Florida, who were seeing the value for housing cratering in areas of Miami near the Zika virus outbreak,” Adams Waldorf said. “Grandparents in Florida began donating to my research program, because their adult children were canceling visits to Florida based on fear of acquiring Zika virus.”

This fear was sufficient to cripple real estate and tourism in Florida, creating a crisis directly linking the virus with economic disruptions. A part of the economy that employs more than a million people and accounts for more than a billion dollars in economic activity had officials deeply worried. A decline in birth rates and an increase in medication abortion in Central and South America reflected the same worries of many American women and young families, who were trying to get pregnant.

The Zika virus outbreak also led to one extremely unusual incident in which the U.S. Central Intelligence Agency approached Dr. Adams Waldorf about the threat of bioterrorism from Zika.

“The CIA was concerned at the time that bad actors might be intentionally spreading Zika virus in the U.S. to create social and economic havoc in Florida and Texas,” Adams Waldorf said. “But this threat isn’t a complex international spy mystery. It’s about sick people getting on planes. This is why studying viruses that cause fetal birth defects is so important for our national security. They might seem unimportant and faraway, but they are literally in our backyard.”

The Adams Waldorf Lab is now studying the ways that fetal brain injury from Zika and other viruses can be detected during a pregnancy, which was a flash point for women who wanted to get pregnant or were currently pregnant during the Zika epidemic. Reassuring pregnant women that their pregnancies were healthy would have gone a long way to bolstering public health during this epidemic.

Government officials chose to spray areas of Miami, where Zika virus infected mosquitoes had been identified to eliminate the danger that it posed to Florida citizens. Fortunately, Zika virus was eliminated in Florida through these efforts, but the risk remains for a new epidemic.

Zika virus is now present in mosquitos and other animals throughout South and Central America, Dr. Adams Waldorf said. Once there are enough children in these populations that lack Zika virus immunity, because they weren’t alive or didn’t get infected in the 2015-2018 epidemic, there may be a new Zika virus epidemic.

The Adams Waldorf Laboratory is also identifying other viruses that could wreak havoc on public health and the economy. For example, the Oropouche virus is spread by midges and mosquitos and can be passed from a pregnant woman to their fetus. Oropouche has been associated with birth defects and stillbirths, similar to Zika. But the overall risk is still unknown and needs further study.

Studying birth defects caused by viruses is central to both public health and national security. But that can’t happen without researchers doing the basic science that will give public policymakers the information they need to make informed decisions.

Cuts to Research Funding Threaten Medical Breakthroughs

WaNPRC Director Deborah Fuller and University of Washington Assistant Professor of Microbiology Patrick Mitchell team up in this article in The Conversation to explain how funding cuts affect medical breakthroughs.

They explain how the termination of hundreds of active research grants could mean fewer clinical trials, fewer new treatments and fewer lifesaving drugs. Labs will likely shut down, jobs will be lost, and the process of discovery will stall.

Grant to Study Colored Light for Pain Management

Jim Kuchenbecker and Jay Neitz are part of a collaborative team that has been awarded a highly competitive, nearly $8 million grant provided by the National Institute of Neurological Disorders and Stroke (NINDS).  The grant will fund groundbreaking research titled: “Neural Mechanisms of Colored Light-Driven Analgesia.” The group’s research explores the use of colored light to modulate pain pathways in the brain. This work represents an innovative approach to managing pain without the use of opioids, contributing to a vital area of research aimed at addressing the ongoing opioid crisis. The project is set to span five years. It will involve a multidisciplinary team of investigators, including Jay Neitz, PhD, vision neuroscientist, and Jim Kuchenbecker, PhD, bioengineer, and vision scientist at the University of Washington and two other institutions, Norman Taylor, MD, PhD at the University of Utah and Matt Mauck at the University of North Carolina. This grant, a part of the NIH HEAL Initiative, supports collaborative approaches to generate new mechanistic knowledge to improve pain management.

In clinical studies, colored light has been shown to be more effective in ameliorating pain than white light when compared at equal brightness. This implicates color-opponent circuitry in the primate retina in the neural mechanism of light-driven analgesia. Because of the unique mechanisms responsible for carrying color information in humans shared only by other primates, nonhuman primate research has been essential color research. During the last century, it was assumed that the neurons in the retina carrying color information were involved in conscious color perception, mediating the sensations of red, green, blue, and yellow. However, in 2005, Dennis Dacey and colleagues at the University of Washington discovered that retinal ganglion cells involved in non-image-forming visual capacities, including synchronizing our internal biological clock to the external day, are color-opponent making them sunrise-sunset detectors sensitive to the change in the color of the sky from blue to orange when the sun is at the horizon.

Since then, Kuchenbecher, Neitz, and their colleagues in the UW Department of Ophthalmology have discovered that multiple types of neurons in the primate retina carry color information integrating environmental light cues and relaying them to various brain centers. Their influence extends far beyond circadian entrainment, encompassing sleep, mood, cognition, metabolism, and overall health. Understanding these diverse roles has significant implications for therapies targeting light exposure to improve health and well-being. These include influencing pain perception and sensitivity.  This may make sense in terms of primate evolution when being able to endure pain may have been critical to survival.  After the sun goes down, an injured primate ancestor exposed to the elements in the great outdoors is subject to many life-threatening hazards, including hypothermia, starvation, or being killed by predators.  Seeing the color of the sunset might indicate to an injured primate ancestor that getting back to safety is more important than focusing on the pain they are experiencing. Signals from color-sensitive ganglion cells may communicate with ascending pain centers to ameliorate pain until the animal is safe at home.  The proposed research will illuminate the underlying mechanisms and has the promise to provide new strategies for controlling pain using light.

Do You Need a Measles Booster?

WaNPRC Director Dr Deborah Fuller spoke with Everyday Health about the efficacy of MMR vaccines and whether or not adults need a booster.

The current measles outbreak that has killed at least two people so far in Texas and New Mexico were in unvaccinated people, one child, one adult. The Centers for Disease Control says the two-dose regimen of the measles, mumps, and rubella vaccine is 97% effective against measles.

“Most people who have received two doses of the MMR vaccine do not need a measles booster shot, but some specific individuals may benefit,” Dr Fuller said, adding that it’s vital to know your vaccination and health history, and whether you may benefit from an MMR vaccine booster if you’re in a vulnerable group, such as people who only had one does of the MMR vaccine or who were vaccinated when a less effective vaccine was used.

The CDC says measles does not have an antiviral treatment, and vaccines are the best defense against infection.

New Paper: HIV May Increase Risk of Prolonged Zika Infections

A new paper co-authored by three WaNPRC researchers in Frontiers in Immunology indicates that people with HIV may be at greater risk for prolonged Zika virus (ZIKV) infections, and that people vulnerable to mosquito-borne illnesses like Zika would benefit from protections like vaccines. 

The paper, “Persistent innate immune dysfunction and ZIKV replication in the gastrointestinal tract during SIV infection in pigtail macaques,” suggests that people living with HIV may be at greater risk for prolonged Zika virus infections and that the virus stayed in the body longer. 

Dr. Megan O’Connor, Director Deb Fuller and former WaNPRC researcher and current affiliate Dr. Michael Gale contributed to the paper. The study looked at nonhuman primates (NHPs) co-infected with simian immunodeficiency virus (SIV) and Zika, the disease involved in a well-known outbreak in the Americas in 2015-2016 that infected tens of thousands of people and caused symptoms ranging from a rash and fever to microencephaly in babies (an abnormally small head), and even death. In the study NHPs had a harder time fighting off Zika, and the Zika virus stayed in their body longer, especially in places like the gut.  

They wrote: “Collectively, these findings uniquely suggest that untreated SIV infection may promote inflammatory cellular innate responses and create a state of persistent immune activation that contributes to prolonged ZIKV viremia and persistence in the gastrointestinal tract. Furthermore, these results suggest that people living with HIV and other immunocompromised individuals could be at higher risk for prolonged ZIKV infection, potentially extending the window of ZIKV transmission. These insights highlight the importance of including people living with HIV in strategies for deploying vaccines and treatments against ZIKV.” 

In other words, this indicates that people living with HIV, who have weaker immune systems, might have a harder time fighting off Zika, and it could stay in their bodies for a longer time. The researchers said this means public health officials need to make sure such people get treatments, such as vaccines, to help them fight off Zika more effectively. 

You can read the entire paper, here. 

Dr. Fuller was appointed director of WaNPRC in late last year. 

Dr O’Connor was appointed in February to the University of Washington faculty as Assistant Professor in the Department of Laboratory Medicine and Pathology.  She is a Core Scientist in the WaNPRC Infectious Disease and Translational Medicine Unit and focuses on HIV viral co-infections with the goal of improving treatment and vaccine strategies for people living with HIV and other immunocompromised people.

Director for Research Lands Zika Papers in The Lancet

WaNPRC’s Interim Assoc. Director for Research, Kristina Adams Waldorf collaborated on a four-part series with other researchers in The Lancet Infectious Diseases and The Lancet Microbe. The series identified key research priorities needed to detect and mitigate the threat of future mosquito-borne Zika virus outbreaks. 

Dr Adams Waldorf is a leading researcher on Zika virus, which emerged in the Americas in 2015 and resulted in a devastating epidemic of infants born with small heads (microcephaly) and other severe congenital malformations. 

The four manuscripts focus on: Zika research priorities for preparedness and response, vaccines and monoclonal antibodies, non-human primate models of Zika virus, and sharing of specimens and data to accelerate Zika research and development. 

In the paper in which she was the senior author, the role of NHP models in research and developing zika countermeasures, she notes that Zika virus remains a threat to global pregnancies, is now endemic in 92 countries, and can be found in mosquitos in another 60 countries. 

Dr Adams Waldorf writes that developing therapeutics against Zika requires nonhuman primate research to mirror the physiology of human pregnancies.  NHP pregnancy is “remarkably similar to human pregnancy” she writes, from the interface between the fetus and mother to the fetal development. 

NHPs have emerged as the gold standard model for understanding the pathogenesis of ZIKV infection in humans and human pregnancy. Accelerating research and discovery on ZIKV will continue to rely on the availability of diverse non-pregnant and pregnant NHP models that can address different aspects of viral pathophysiology,” she writes. 

Another paper in the series notes that there are no licensed Zika vaccines or monoclonal antibodies currently available, which means world’s populations, particularly those who may become pregnant, are unprotected from Zika transmission, infection, and disease. 

Dr Adams-Waldorf’s paper can be found here: Role of non-human primate models in accelerating research and developing countermeasures against Zika virus infection published in The Lancet Microbe.  https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(24)00298-2/fulltext 

The other papers are: 

Zika virus vaccines and monoclonal antibodies: a priority agenda for research and development: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00750-3/fulltext 

Zika virus: advancing a priority research agenda for preparedness and response:  https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00794-1/fulltext 

Specimen and data sharing to advance research and development on Zika virus:  https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(24)00325-2/fulltext