Category: News

Ongoing studies with Umoja Biopharma, HDT Bio, and the Allen Institute

Nonhuman primate studies are crucial in biomedical research, particularly developing new therapies. The pigtail macaque monkeys at the Washington National Primate Research Center share a closer genetic and physiological resemblance to humans than other animal models. This similarity allows researchers to predict better how a therapy might behave in humans, offering valuable insights into potential efficacy and safety.

Such is the case with Umoja Biopharma’s VivoVec platform for chimeric antigen receptor T (CAR-T) cell therapy. In this in vivo study, the researchers observed the activation and expansion of CAR-T cells in the monkeys and their impact on target cells. The researchers, supported by the animal care and research staff at WaNPRC, compared the CAR-T cell expansion and persistence in monkeys with data from previous studies on ex vivo CAR-T therapies in similar primate models. This provided valuable insights into the platform’s potential advantages.

Overall, this public/private partnership is a critical bridge between preclinical research and clinical translation, providing essential data on the safety, efficacy, and feasibility of new therapies like Umoja’s VivoVec platform for CAR-T cell therapy.

Scientists at the Allen Institute celebrate their global collaboration in mapping the hundreds of billions of cells in rodents, macaque monkeys, and human brains.  They are mapping them by their type and function as part of the BRAIN Initiative® Cell Atlas Network, or BICAN, with financial support from NIH’s B.R.A.I.N. Initiative, or Brain Research Through Advancing Innovative Neurotechnologies® Initiative.

The WaNPRC, by providing the Allen Institute’s NHP models, is helping to bridge the knowledge gap between rodent models and humans.

Dr Randy Kyes, chief of the Global Conservation, Education & Outreach unit at the WaNPRC, and his Nepali colleagues wrapped up their 21st year of field training in Kathmandu, Nepal, before gaining some altitude in their annual climb up to their field sites in Langtang National Park. This was a return the site of a devastating  7.8 magnitude earthquake and resulting landslide in April of 2015.

Kyes and his Nepali colleagues highlighted their dedication and collaboration over the past two decades in a two-day photo exhibit titled “Langtang Through the Lens of Field Researchers.” The event was hosted at the Central Library of Tribhuvan University (TU) and sponsored jointly by the library itself, and the university’s Department of Library and Information Science, along with the Central Department of Zoology.

The exhibition provided a visual journey into the heart of the Himalayas and served as a celebration of over two decades of partnership and collaborative research, training, and outreach in the Langtang region.

At the heart of this celebration were the tireless efforts of dedicated field researchers, including long-time collaborators like Prof. Mukesh Chalise and past students turned colleagues, Dr. Narayan Koju and Dr. Laxman Khanal. In a moving speech at the opening of the event, Kyes also expressed his gratitude to the local residents of Langtang for their years of support noting that this exhibition is dedicated to their dear friends who were lost in the terrible 2015 earthquake and landslide.

Supported in part by OEI, USA, the exhibition not only showcased the beauty of Langtang, but also underscored the importance of these photographs as valuable sources of information for future research endeavors. It served as a reminder of the enduring impact of collaborative efforts in preserving and understanding our natural world.

This collaboration started in 2000 when I first visited Nepal and met with Mukesh Chalise, who became my long-time colleague. Two of our past field course students now colleagues, Laxman Khanal and Narayan Koju, are continuing this long collaboration – leading the way into the future.

 

Friday, February 2, 2024:

Midway through a thrilling three-week macaque distribution survey in Sumatra, spearheaded by Dr. Entang Iskandar from the Primate Research Center (PSSP) at IPB Bogor University, Randy’s journey took an exciting turn. Navigating through the verdant landscapes of the Aceh province, they stumbled upon two substantial groups of macaques, featuring both pig-tailed macaques (Mn) and long-tailed macaques (Mf), congregating along the roadside.

It is a real pleasure to be assisting my long-time colleague Dr. Entang Iskandar who is leading this important study.  I’ve worked closely with Entang and PSSP-IPB for over 30 consecutive years and I believe this project represents truly foundational work – helping to fill in the gaps regarding macaque distribution and target locations for in-depth population surveys.

Saturday, January 27, 2024:

On the fifth day of their collaborative three-week distribution survey in Sumatra, Dr. Entang Iskandar and Randy continued north as they delved into the northern half of the island for Phase 2. Their expedition led them to Taman Kera, Sumatra Utara, where they encountered sizable Mn and Mf macaque groups.

Wednesday, January 24, 2024:

Dr. Kyes expresses his pleasure at returning to Indonesia, once again joining forces with Dr. Entang Iskandar for the second phase of their macaque distribution survey. The collaborative spirit is resonating as they work towards unraveling the nuances of macaque populations of pig-tailed and long-tailed macaques in Sumatra.

Monday, December 25, 2023:

Looking forward to 2024, Randy and research scientist Dr. Pensri (“Elle”) Kyes, along with partners at Mahasarakham University and Mae Fah Luang University promise to delve deeper into the intricate dynamics of the relationship between humans and wild monkeys. The journey continues, and their shared dedication to bridging the gap between humans and primates propels them into the new year with enthusiasm and determination.

Key Details: Pig-Tailed Macaque Monkeys

Species: Macaca nemestrina

Other common names: southern pigtail macaque, Sundaland pig-tailed macaque or Sunda pig-tailed macaque.

Geographic locations of wild populations: Indonesia, Malaysia, Thailand.

Import status: All pigtails at the Washington National Primate Research Center are purpose-bred for research.

Conditions negatively impacting wild pig-tailed macaque populations: Human encroachment into natural habitats, climate change, pollution, oil and gas production, human recreational activities, hunting and trapping.

Source of pig-tailed macaques studied at the University of Washington: All pig-tailed macaque monkeys involved in research at the University of Washington were bred expressly for involvement in health research.

Diseases and Disorders That Require the Study of Pig-Tailed Macaque Monkeys

• Women’s Health – Like humans, pig-tailed macaques experience menopause, menstrual cycles and give birth throughout the entire calendar year. We also share similar reproductive anatomy making these animals an important model to combat illnesses, such as chlamydia, that impact women around the globe.
• Health Issues Associated with Premature Birth – Research in pig-tailed macaques helps researchers understand and counteract premature birth and neonatal hypoxia. Neonatal hypoxia, the tragic result of oxygen deprivation shortly before or after birth, affects roughly 2-3 out of 1,000 live human births in the U.S. each year.
• Zika Virus Research – The study of Zika virus transmission during pregnancy occurs in pig-tailed macaques because their immune system is similar to humans.
• HIV/AIDS Research – HIV, the virus that causes AIDS, impacts the brains of both humans and pig-tailed macaques in a similar way. People with HIV are living longer, healthier lives thanks to past research in pig-tailed macaques.
• Valley Fever Research – Like humans, pig-tailed macaques are uniquely susceptible to Valley fever, a disease caused by inhaling a soil-dwelling fungus. This means these animals play a crucial role in the fight against Valley Fever, a growing health threat exacerbated by increasing global temperatures.
• Aging and Social Behavior Research – There is growing evidence that pig-tailed macaques are a highly valuable research model for the study of aging and certain social behaviors where animal/human parallels exist.

Generated in collaboration with Americans for Medical Progress 

Already holding the esteemed title of Clare Boothe Luce Assistant Professor of Electrical & Computer Engineering, Dr. Amy Orsborn, Neuro core scientist at WaNPRC, was among three University of Washington (UW) faculty selected to comprise this inaugural cohort by the Washington Research Foundation (WRF). The UW Department of Electrical & Computer Engineering describes the fellowships as, “…honoring those who have research emphasis in neuroscience fields, a record of demonstrating Diversity, Equity and Inclusion (DEI) initiatives, and the capacity to bridge disciplines and domains.”

Amy’s work is groundbreaking, merging her computational expertise with innovative approaches in experimental systems neuroscience. The result? Fresh, fundamental insights into how neural circuits master the art of learning. Her mission? To shed light on the intricate mechanisms behind learning within expansive brain networks, all with the ultimate aim of enhancing our ability to manipulate cortical dynamics for treating neural injuries and disorders. Learn more about the Fellowship and the other recipients, Drs. Gabe Cler and Sam Golden, within the Office of Research’s announcement, “Three Faculty Chosen for the Washington Research Foundation Ronald S. Howell Distinguished Faculty Fellowship.”

A big thanks to the Washington Research Foundation @wrfseattle for their support! It’s a huge honor to receive an award focused on things I value so much: interdisciplinary research & teaching/outreach to make science a more inclusive and equitable place.

Beyond her research and teaching, Amy is deeply involved in the Women in Science and Engineering program. She’s also the co-founder of the Women in Neural Engineering group, dedicated to advancing the careers of women in the field. Her commitment to diversity and equity in science and engineering is crystal clear.

The goal of this project is to define the molecular and cellular mechanisms by which IL-15 programs protective immunity with the RhCMV-SIV vaccine to inform our understanding of HCMV-HIV vaccine immunity against HIV.

The world is in need of an effective HIV/AIDS vaccine, and the cytomegalovirus (CMV) vector-based HIV/SIV vaccine featured in our studies is highly efficacious and durable to uniquely mediate viral “replication arrest” efficacy in the Rhesus Macaque-SIV model. Vaccine immunity is mediated by unconventional MHC-E-restricted CD8+ T cell responses and induction of IL-15, which correlate with vaccine protection. The work proposed in this application will reveal the molecular mechanisms of immune programming by the CMV-based vaccine and IL- 15 actions to inform human testing of this vaccine concept in ongoing and future phase I/II trials.

NIH P01 AI177688:     $8,472,008

 

As seen in October 2023 issue:
The disease hits farmworkers and outdoor laborers disproportionately hard.

The article discusses the growing threat of Valley fever, a fungal disease caused by Coccidioides, in the western United States, particularly in the San Joaquin Valley of California. Valley fever thrives in dry, dusty environments and can be inhaled as airborne pathogens. It is characterized by symptoms such as coughing, fevers, body aches, fatigue, rashes, and appetite loss. The disease disproportionately affects vulnerable populations, including Latino, Asian, and Native American communities, due to their frequent exposure to dusty outdoor locations. Many of those affected lack access to basic healthcare and are afraid to seek medical help due to concerns about employer retaliation or deportation.

The article highlights that Valley fever is underreported, underdiagnosed, and underfunded, with limited research on the disease. Researchers are working to better understand its spread and develop treatments and vaccines. Climate change and environmental factors, such as increased dust exposure, are contributing to the spread of Valley fever, and there is concern that it could extend into new regions in the future.

One potential benefit of a Valley fever vaccine is that it could be a one-and-done kind of thing—unlike those for influenza or even tetanus, which must be updated regularly. According to studies by microbiologist Deborah Fuller of the University of Washington School of Medicine, people who get Valley fever develop lifelong immunity. That, Fuller says, “is the golden egg.”

Fuller’s research team is actively working on developing both DNA and RNA-based vaccines. These vaccines are designed to stimulate the body to produce specific proteins that can trigger a strong immune response. What makes these vaccines particularly valuable is that they have the potential to do more than just combat Valley fever. They could also serve as a valuable tool for researchers to gain a better understanding of how the immune system responds to other fungal diseases. This research could ultimately lead to improved treatments for a range of fungal infections, providing valuable insights into the field of fungal disease immunology.

Efforts are also underway at both the local and federal levels to address the threat of Valley fever, with some researchers working on vaccines for humans, building on the success of a vaccine for dogs. Funding for Valley fever research has increased in response to rising incidence rates, but there is a long way to go in terms of awareness, diagnosis, and treatment of this fungal disease, especially among vulnerable populations like farmworkers.

Related:
https://news.nau.edu/valley-fever-collaborative/
https://pubmed.ncbi.nlm.nih.gov/37730871/

research funding opportunities

 

• UH3MH120095 (Ting/Lien/Levi/Kalume, MPI) – Cell type selective tools to interrogate and correct non-human primate and human brain circuitry neurophysiology of disjunctive saccades (w/ Allen Institute)
• R01EY035921 (Walton, PI) – Neurophysiology of Disjunctive Saccades
• R01AI17677 (Adams Waldorf/Gale, MPI)– Impact of Zika virus infection on fetal innate and adaptive immunity
• R01AI175459 (Frueh/Sacha, MPI; Gale, Co-I)– Non-canonical epitope presentation and antigen processing by MHC-E (w/OHSU & ONPRC)
• R44 AI186932 (Bagley, Fuller, MPI) – Enhanced seasonal influenza vaccine targeting variable and conserved antigens (w/Orlance, Inc.)
• BAA-HHS-NIH-NIAID-BAA2023-1 (Robb, PI; Fuller, Co-I) – Development of a delta-cps1 live attenuated vaccine against Valley Fever (Coccidioidomycosis) (w/Anivive, Inc.)
• R33AI161811 (Kahndhar, PI; Fuller, Co-I) – Engineering the immune response of a self-replicating and adjuvanting RNA HIV-1 vaccine (w/HDT Bio)

 

 

Dr. Cynthia Derdeyn & Emory University
NIH R01-AI174979        $4,002,880

The National Institutes of Health (NIH) is providing financial support to Dr. Derdeyn and her collaborators at Emory National Primate Research Center (ENPRC) for their research on HIV vaccines before human testing. They have demonstrated that the vaccine triggers strong levels of protective antibodies capable of preventing infection. Additionally, they have identified the specific vaccine components that these antibodies target. These discoveries are driving the development of new approaches to enhance protection.

The similarity between the protective antibodies produced in response to the vaccine in both monkeys (nonhuman primates or NHPs) and humans is being illustrated. By monitoring the development of these antibodies, the Derdeyn Lab is gaining comprehensive insights into this complex process. Their work underscores the value of the monkey model in fully comprehending this mysterious mechanism. Their findings, demonstrating the production of similar protective antibodies in both monkeys and humans, are advancing efforts to create an effective HIV vaccine.

 

Dr. Michael Gale, Jr.
NIH P01 AI177688       $8,472,008

The goal of this project is to define the molecular and cellular mechanisms by which IL-15 programs protective immunity with the RhCMV-SIV vaccine to inform our understanding of HCMV-HIV vaccine immunity against HIV.

The world needs a good vaccine for HIV/AIDS, and the Gale Lab is studying a candidate using a virus called cytomegalovirus (CMV). It’s very effective and long-lasting at stopping the virus from multiplying in the Rhesus Macaque-SIV model. This vaccine works by activating a type of immune response that’s a bit unusual, and it also increases the levels of a protein called IL-15, which helps protect against HIV.

They are seeking to figure out exactly how this vaccine and IL-15 work together to create protection and to use that knowledge to test the vaccine in people in phase I/II trials. In simpler terms, they’re trying to understand how a specific vaccine using CMV and IL-15 can protect against HIV, then building on this information to develop better HIV vaccines for humans.

 

Dr. Megan O’Connor
NIH R21AI170094-01A1       $706,000
NIH R01HL165933-01A1       $3,876,310 
Dr. O’Connor‘s R21 study aims to understand how a new type of COVID-19 vaccine works in a monkey model of HIV/AIDS, which mimics immune problems. The information the lab is gathering will help make this vaccine better for global use, even in places with fewer resources, and for people with weakened immune systems, like those with HIV.

With the R01 funding, the O’Conner Lab is studying how HIV affects our immune system and gut bacteria when it comes to COVID-19. Through their work involving monkeys with HIV, they are learning how our immune system affects COVID-19 in the lungs and how having a weaker immune system can make COVID-19 worse.

 

Dr. Amy Orsborn
NIH R01NS134634-01       $701,214

Dr. Amy Orsborn‘s project aims to make brain-computer interfaces (BCIs) better. BCIs can help paralyzed people move, but they have problems lasting a long time and working well in different situations. This is because our brains change when we use BCIs a lot, and this affects how well they work. The Orsborn Labs wants to understand these changes and use them to make BCIs more reliable. We will use monkeys to study how their brains change when they control a computer cursor with their thoughts. We will also use special implants to see what’s happening in their brains over 10 days.

The laboratory has three main goals:

1. See if the way they program the BCI (called the decoder) affects how the brain organizes information (called the encoder). This can make BCIs more resistant to signal loss (when the brain can’t send signals) and changes in tasks.
2. Check if the decoder also influences how specific the encoder is to certain BCI movements. This can make BCIs better at adapting to different tasks.
3. Develop new computer methods that can make BCIs more robust without making them perform worse. By studying these things, they hope to make BCIs using brain plasticity to work better for a long time and in different situations.

 

Dr. Anitha Pasupathy
NIH U01 NS131810-01        $3,315,014

Dr. Pasupathy and her collaborators’ main aim is to deeply and precisely understand how different parts of the primate brain work together when making decisions based on what they sense. They want to create detailed maps that show how different areas of the brain communicate with each other down to the level of individual cells.

They’re going to create new methods that will help them:

1. Accurately find linked brain cells in different parts of the brain, both near the surface and deep within it.
2. Use advanced scanning technology and special recording devices to see and understand how these brain cells work in larger groups.
3. Study how these groups of brain cells work together while animals do tasks that are relevant to their natural behaviors.

By doing this, they hope to learn how different parts of the brain talk to each other and combine what they sense and know to help animals make sense of their surroundings. This research will also help us understand and develop ways to treat brain problems that affect how we recognize objects or how different parts of our brain communicate, like what happens in conditions like agnosia or autism.

 

Dr. Dorothy Patton
NIH R01-AI175153-01        $5,084,750

Drs. Dorothy Patton and Lucia Vojtech are planning to study whether a type of bacteria, called C. trachomatis (CT), that causes infections in the rectal area might actually protect against infections in other parts of the body, like the genital area. They’ve seen an increase in these rectal infections in clinics that deal with sexually transmitted infections, but they’re not sure how these infections affect the body’s ability to fight off the bacteria or prevent future infections.

In previous studies with mice, researchers found that when the animals were infected with a similar bacteria in their rectal area, it made them less likely to get infected in their genital area. This suggests that a rectal infection might help the body’s immune system learn how to defend against infections in different areas. However, it’s not known if this also happens in humans when they naturally get infected with CT.

To find out, researchers are using a group of pigtail macaques, which have similar responses to infections as humans. They’re infecting these monkeys with CT in their rectal area and then observing if this protects them from getting infected in their genital area later on. At the same time, they’re also studying how the immune system responds to rectal infections with CT in humans.

By comparing the results from the monkey and human studies, the researchers aim to see if a rectal infection triggers a stronger immune response that can better protect against future infections compared to infections in the genital area. This information could help them develop vaccines that provide better protection against CT infections in humans, especially in the genital area, and prevent the most severe consequences of these infections.

 

More new funding:

• R01 AI174979 (Derdeyn, PI) – Tracking the evolutionary trajectory of neutralizing antibodies following BG505 SOSIP immunization in rhesus macaques, $822,777 (current FY)
• R21AI168739  (Shears, PI)** – Malaria vaccine evaluation in a novel infant NHP challenge model, $353,000
• R44AI179440 (Frizzell/Fuller, MPI) – Clinic-ready MACH-1 Gene Gun for Delivery of a Universal Influenza DNA vaccine, $996,500
• U19AI166058-supplement (Keim PD, Fuller Project PI)  – Early In Vivo Expressed Antigens and their Role in Virulence, Immune Response and Vaccines for Coccidioidomycosis, $1,390,215
• R01AI170214 (Peterson, PI)** – Developing Durable, Env-Boosted CAR T Cells for HIV Cure, $893,464
• R01AI174304 (Lieber/Kiem, MPI) – In vivo HSC gene therapy using a multi-modular HDAd vector for HIV cure, $685,904
• amfAR, The Foundation for AIDS Research (Lieber/Kiem, MPI), – Portable gene therapy treatment, $480,000

 

 

The Washington National Primate Research Center was tapped to serve as the coordinating center to oversee the combined pledge of funds from the NPRCs in California, Georgia, Louisiana, Texas, Washington and Wisconsin totaling $30,000.

This aid will arrive in Puerto Rico by way of a container ship with vital supplies and equipment. The NIH is facilitating these operations, and FEMA is prioritizing urgent animal support supplies in order to avoid some of the supply chain backups that have plagued ground distribution in the aftermath of Hurricane Maria.

 

60 MINUTES – NEWSMAKERS
On Monkey Island, scientists have rare access to more than 6 decades of biological, behavioral data

UW Medicine Newsroom asked faculty experts to offer a summer outlook on COVID protection.

Virologist and WaNPRC Associate Director for Research, Dr. Deborah Fuller, and Immunologist Dr. Marion Pepper provide insights into the current status of COVID protection as the disease continues to impact respiratory infections.

uw medicine newsroom