Marburg vaccine tested at Texas Biomed deployed to Rwanda

  • Doses of an investigational Marburg vaccine have been sent to Rwanda to combat outbreak
  • Texas Biomed partnered with Sabin Vaccine Institute to perform nonclinical testing of the Marburg vaccine

SAN ANTONIO (Oct. 16, 2024) – Texas Biomedical Research Institute (Texas Biomed) conducted early tests of the investigational Marburg vaccine now being deployed to Rwanda to help control the outbreak that began in late September.

The vaccine candidate is being developed by Sabin Vaccine Institute, which delivered 1,700 doses in two separate shipments to Rwanda – the first within nine days of the outbreak being declared.

As of October 15, the Marburg virus outbreak in Rwanda has infected 62 people and caused 15 deaths, according to the Rwandan Ministry of Health. Marburg is part of the same family of viruses as Ebola virus, and similarly causes hemorrhagic fever and has a fatality rate of up to 88%.

“We are grateful that our partners at Sabin have been working to develop a candidate Marburg vaccine so that we can protect people from this very deadly virus,” says Ricardo Carrion, Jr., Ph.D., the Director of Maximum Containment Contract Research at Texas Biomed. “We are proud to have played a role in the studies needed to advance the vaccine to human trials.”

Early tests demonstrating safety and efficacy were completed at Texas Biomed and elsewhere in animal models, which are essential before any vaccine or therapy progresses to clinical trials in humans.

There is currently no approved vaccine or treatment for Marburg virus. Sabin’s vaccine candidate is currently in Phase 2 clinical trials in Kenya and Uganda. At the request of Rwandan officials, Sabin mobilized quickly to provide vaccine doses and partner with the Rwanda Biomedical Centre to launch a rapid response Phase 2 open-label study there. The aim is to vaccinate adults at the highest risk, beginning with healthcare providers, according to a Sabin press release. Rwanda health officials report more than 770 vaccine doses have been administered as of October 15.

“Infectious disease outbreaks are unfortunately occurring more frequently. Texas Biomed is committed to developing countermeasures like vaccines and antibody therapies proactively, to ensure they are ready to be deployed as quickly as possible when an outbreak is declared,” says Cory Hallam, Ph.D., Executive Vice President, Applied Science and Innovation at Texas Biomed. “We applaud our partners for the global cooperation that has seen them launch important clinical trials so quickly after the outbreak was confirmed.”

Research and development of the Sabin vaccine candidate have been largely funded by the U.S. Biomedical Advanced Research and Development Authority (BARDA). Sabin also acknowledges NIAID’s Vaccine Research Center and its manufacturing partner, ReiThera, for their continued support.  

More Information

Marburg vaccine tested at Texas Biomed moves to Phase 2 clinical trials

Sabin Vaccine Institute Delivers Marburg Vaccines to Combat Outbreak in Rwanda

Funding information:

This project has been funded in whole or in part with Federal funds from the Department of Health and Human Services, Biomedical Advanced Research and Development Authority, Office of the Assistant Secretary for Preparedness and Response, Office of the Secretary under Contract No. 75A5011900055 and 75A50123C00010.

###

About Texas Biomed

Texas Biomed is a nonprofit research institute dedicated to protecting the global community from infectious diseases. Through basic research, preclinical testing and innovative partnerships, we accelerate diagnostics, therapies and vaccines for the world’s deadliest pathogens. Our San Antonio campus hosts high containment laboratories and the Southwest National Primate Research Center. Our scientists collaborate with industry and researchers globally, and have helped deliver the first COVID-19 vaccine, the first Ebola treatment and first Hepatitis C therapy.

Dr. Erika McAfee joins Texas Biomed’s veterinary team 

Dr. Erika McAfee has joined the veterinary team at Texas Biomed

Even after spending years as an avid Animal Planet viewer, Erika McAfee, MLAS, D.V.M., had no idea she would end up being inspired to work with primates in biomedical research.  

“I always enjoyed biology and animal science, but I started out thinking I wanted to do human orthopedic medicine. After completing a human medical program, I realized it wasn’t for me,” says Dr. McAfee. “I decided I really wanted to work with primates, and throughout my clinical years in vet school, I focused as much as possible on primate medicine.” 

Following a three-week externship at Texas Biomed earlier in 2024, Dr. McAfee officially joined the team as Faculty Veterinarian in August. 

Prior to her time at Texas Biomed, Dr. McAfee served as a postdoctoral fellow and laboratory animal medicine veterinary resident at the Salk Institute for Biological Studies in San Diego, CA. She holds a Doctor of Veterinary Medicine from Midwestern University College of Veterinary Medicine, a Master of Laboratory Animal Science from Drexel College of Medicine, and a Bachelor of Science from Spelman College. 

Dr. McAfee says that people are intrigued when they hear that she works with primates. 

“Everyone assumes that because I’m a veterinarian I work with cats and dogs. The fact that I work with primates is really interesting for a lot of people and I get a chance to educate them about how much care and enrichment our animals receive,” she says. 

During her time as a research assistant at the University of Pennsylvania, Dr. McAfee was part of the team that worked on developing the one of the first FDA-approved treatments for a rare genetic disorder called fibrodysplasia ossificans progressiva, in which bone gradually replaces muscle and connective tissue.  

“The work was very rewarding, but human medical research isn’t where I’m supposed to be,” says Dr. McAfee. “I am very interested in translational medicine, which is what drew me to working with primates.” 

Translational science aims to improve the process of turning research into health solutions, primarily with the help of animal models. These models allow researchers to study disease mechanisms and evaluate the safety and efficacy of potential treatments prior to advancing to studies in humans.  

Dr. McAfee, who completed her residency training at Salk Institute for Biological Studies, estimates that 95% of her clinical case management was focused on marmosets. Texas Biomed is home to the largest colony of marmosets dedicated to aging and infectious diseases research in the nation. 

“Coming to Texas Biomed, I’ve been excited to work with vastly different species, especially the baboons, which I am looking forward to getting to know better,” she says. 

Texas Biomed’s Attending Veterinarian Kathryn Shelton, D.V.M., Ph.D., says, “Dr. McAfee brings a wealth of knowledge and experience to Texas Biomed. Her expertise and dedication to veterinary medicine will be invaluable to our institution and we are excited to have her on board and look forward to her contributions.” 

Promising TB therapy safe for patients with HIV

Texas Biomed researchers complete critical preclinical study to advance potential tuberculosis therapy toward human clinical trials

SAN ANTONIO (September 27, 2024) – A therapy showing promise to help control tuberculosis (TB) does not interfere with combined antiretroviral therapy (cART), according to research by Texas Biomedical Research Institute (Texas Biomed).

“This is an important hurdle that this host-directed therapy had to clear in order to help patients battling both HIV and TB,” said Texas Biomed Professor Smriti Mehra, Ph.D., who led the study recently published in the peer-reviewed journal JCI Insight.

TB is responsible for more than 1.3 million deaths worldwide every year. Dr. Mehra and her team have been investigating a therapy currently used in cancer as a potential treatment for patients with drug-resistant TB and/or comorbid HIV. While many cases of TB can be controlled with months of antibiotics, the infection can return in people who are immunocompromised as a result of HIV. Now that cART is so effective at controlling HIV, a resurging TB infection can often be deadly to those individuals.

Dr. Mehra is studying a host-directed therapy that blocks or inhibits an immune system protein naturally found in the body. The protein, called IDO (short for Indoleamine-2,3-dioxygenase), normally suppresses the immune system, preventing it from causing excessive inflammation and organ damage. Inhibiting IDO for short intervals of time has led to more successful cancer treatments. Dr. Mehra’s team has previously shown the same approach improves control of TB in conjunction with antibiotics.

This current study in nonhuman primates with both TB and simian immunodeficiency virus, the nonhuman primate version of HIV, showed the IDO inhibitor does not interfere with cART.

Images of cART and cART + IDO Inhibitor
Researchers compare the impacts of cART by itself versus cART plus the IDO inhibitor in lung tissue of nonhuman primates with both TB and SIV. Left: Following just cART, significantly more IDO is detected in pink. Right: With the IDO inhibitor and cART, more immune cells recruited to fight bacteria are observed inside the granuloma, a hallmark structure of TB. Specifically, CD4+ T cells are in green and CD68 proteins expressed by macrophages are in red.

“There was no increase in viral load in animals given cART and the IDO inhibitor, compared with animals only given cART, proving the inhibitor is safe to give to patients with HIV,” Dr. Mehra said.

Now that the researchers have shown the inhibitor works well in conjunction with TB antibiotics and with cART separately, they plan to study how it performs when given in conjunction with both antibiotics and cART together. This treatment regimen is standard for patients with both HIV and active TB. Dr. Mehra said that longer-term studies are also needed to confirm there are no unintended side effects.

The IDO inhibitor is already FDA-approved for use in patients with cancer, which shortens the path to potential approval for patients with TB/HIV when compared with developing a brand-new drug.

###

About Texas Biomed

Texas Biomed is a nonprofit research institute dedicated to protecting the global community from infectious diseases. Through basic research, preclinical testing and innovative partnerships, we accelerate diagnostics, therapies and vaccines for the world’s deadliest pathogens. Our San Antonio campus hosts high containment laboratories and the Southwest National Primate Research Center. Our scientists collaborate with industry and researchers globally, and have helped deliver the first COVID-19 vaccine, the first Ebola treatment and first Hepatitis C therapy.

Texas Biomed and SNPRC welcome Colony Administrator Stanton Gray

SAN ANTONIO (July 23, 2024) — Throughout his 23-year career, Stanton Gray, D.V.M., Ph.D., DACLAM, has sought to improve animal and human health as a veterinarian, colony manager and researcher. Combining both animal care and independent research is often a challenge. Each role requires high levels of dedication, time and energy, and it is rare to find job structures that provide support and protected time for both.

He has found his sweet spot at Texas Biomed and Southwest National Primate Research Center (SNPRC), where he will dedicate one-third of his time to research and two-thirds to managing the center’s three breeding colonies of baboons, rhesus macaques and marmosets.

Colony Administrator and Associate Professor Stanton Gray, D.V.M., Ph.D., DACLAM

“This is what I’ve been working towards and hoping for,” says Dr. Gray, who recently began as both Associate Professor and Colony Administrator. “I am thankful I didn’t have to choose one path or the other.”

Dr. Gray’s expertise lies in working with pedigreed nonhuman primate colonies that have been carefully studied over generations. He uses detailed genetic information to investigate how genetic variation influences diseases like obesity and cancer. Teasing apart genetic factors from environmental influences or epigenetics – changes to the genome that occur throughout life – is difficult. But with nonhuman primates, it becomes possible

to get answers that benefit both animals and humans.

“Pedigreed nonhuman primate colonies have this unique ability to answer questions about complex genetic diseases,” he says. “They can answer questions about how genetics contribute to disease risk in ways that you can’t easily answer with human studies.”

Growing up in Oklahoma City, Dr. Gray had considered attending “human medical school,” but at the encouragement of a friend, checked out veterinary medicine. He worked for a local small animal vet who cared for pets, strays and wildlife, so he built up diverse experience in animal care quickly. He studied zoology and population genetics at the University of Oklahoma and veterinary medicine at Oklahoma State University. After a few years working in private practice in California and Oregon, he decided to go back into research.

“I had the fire in my belly to do research,” he says. “I really enjoy the creativity to pose questions that have not been answered and work towards a better understanding.”

He completed his lab animal medicine residency and a Ph.D. in molecular pathology at Wake Forest University. He served as staff veterinarian at Wake Forest University and then Assistant Director at the Oregon National Primate Research Center. For the last 10 years, he managed a colony of 1,000 rhesus macaques at the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. He also researched conditions that affect both humans and macaques, including colon cancer, Lynch Syndrome, chronic colitis and Chagas disease.

Specifically, he and collaborators Eduardo Vilar-Sanchez, M.D., Ph.D., at MD Anderson and Jeff Rogers, Ph.D., at Baylor School of Medicine, are developing an anti-cancer vaccine that could help reduce colon cancer risk for people with Lynch syndrome. Lynch syndrome is a genetic disease that significantly increases the risk of many types of cancer, especially colon cancer. It involves mutations in “mismatch repair genes,” which normally repair mistakes that occur during DNA replication. The mutations result in non-functional proteins that inhibit this repair function and this is connected with cancers developing at earlier ages.

“Instead of getting colonoscopies in your 40s, if you have Lynch syndrome, you are getting colonoscopies in your 20s,” Dr. Gray says.

Colon cancer is also the most common form of cancer in rhesus macaques. Dr. Gray is seeking to understand if mutations in mismatch repair genes in macaques cause colon cancer through the same or similar pathways as people. If so, rhesus macaques would make excellent models for studying the disease and potential interventions for both humans and animals.

“There seems to be an epigenetic inactivation of the mismatch repair genes. And is that a universal pathogenesis for colon cancer? It seems to be a universal mechanism, but we don’t know for sure,” he says.

He is also studying a common problem that occurs in rhesus macaque colonies: colitis, more commonly known as diarrhea. Understanding and addressing this would be extremely beneficial, especially considering that rhesus macaques make up the majority of nonhuman primates in biomedical research.

“It is such a common problem that clarifying what is going on and developing solutions could have an enormous impact on the overall health of rhesus colonies everywhere,” Dr. Gray says.

Part of the work involves investigating a bacteria called Campylobacter, which is the most common culprit causing diarrhea in people in the U.S. and elsewhere. Dr. Gray is interested in working with others to develop a vaccine to protect against the bacteria for both animals and people.

“Developing a vaccine for Campylobacter is something that has worldwide implications for human and animal health,” Dr. Gray says.

SNPRC welcomes new Attending Veterinarian Kathryn Shelton

SAN ANTONIO (May 9, 2024) — Wearing many hats comes naturally to Kathryn Shelton, D.V.M., Ph.D., DACLAM.

This is a strength she’ll tap into as she joins Texas Biomedical Research Institute (Texas Biomed) and Southwest National Primate Research Center (SNPRC) with not one, not two, but three official roles: Associate Director for Veterinary Resources, Institute Attending Veterinarian and Associate Professor.

Kathryn Shelton
Attending Veterinary Kathryn Shelton, D.V.M., Ph.D., DACLAM

As Attending Veterinarian, she will oversee the Institute’s animal care program, which encompasses more than 2,600 nonhuman primates and 1,800 rodents. As Associate Director, she will help manage the people who care for the animals – about 150 staff members, including animal caretakers, veterinary technicians and veterinarians.

“As leaders in animal care and welfare, we want to continue to raise the bar on best practices,” says Dr. Shelton. “To do that, we have to take care of our team members and ensure their needs are met, so that they in turn can provide the best care for the animals.”

A key part her focus will be to grow SNPRC’s team of veterinarians.

“Not only does Kathryn bring years of nonhuman primate veterinary experience, she also brings extensive leadership experience,” says SNPRC Director Corinna Ross, Ph.D. “I am looking forward to her growing the veterinary program at SNPRC, which will significantly contribute to the resources we provide to investigators and enhance the health and wellbeing of all of our animals.”

Prior to joining Texas Biomed, Dr. Shelton spent 10 years at the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. While there, she enjoyed caring for a wide variety of lab animals and collaborating with researchers across many different studies. She also helped establish a colony of baboons free of specific pathogens.

“I had the really tough job of caring for baby baboons,” she says with a smile.

As Associate Professor, her third hat at Texas Biomed, Dr. Shelton will pursue independent research projects. She is particularly interested in studying how the immune system influences susceptibility to disease and responses to preventative measures like vaccines, and how environmental factors shapes these interactions.

“I am excited to find opportunities for research, especially related to early life events and the long-term effects on the immune system,” she says. “With animals living long lives at Texas Biomed, it provides the opportunity to follow them over time.”

Dr. Shelton’s love of animals runs deep. She is a self-described horse person but does not play favorites when it comes to caring for animals. After attending veterinary school at University of Georgia, she worked as a small animal veterinary clinician for three years. While rewarding, she realized she missed research.

“I really want to be on the cutting edge of knowledge,” she says. “To me, that is the most exciting place to be, when you are trying to answer questions that the answer is fundamentally unknown.”

She decided to pursue a dual graduate degree program in lab animal medicine and a Ph.D. in molecular pathology at Wake Forest University. It was there that she got the taste for juggling multiple research jobs at once.

“I’d be pipetting in the lab, running my experiment, get a page on my pager and have to run across campus to check on a pig,” she recalls. “I remember thinking ‘This is crazy’, but I liked it.”

She passed the lab animal medicine board certification test, becoming a Diplomate of the American College of Laboratory Animal Medicine (DACLAM), and has been combining veterinary care and research ever since.

“I’m very passionate about animal care and welfare, and that goes hand in hand with my passion for the discovery of knowledge for the benefit of humans and animals,” she says.

She is excited to bring that passion to a national primate center where she can support even more research, and join Texas Biomed as it is moving forward with its 10-year strategic plan for growth.

“Texas Biomed has a strong vision for the future and is in a time of change,” she says. “I am excited to be a part of that.”

Zika vaccine safe, effective when administered during pregnancy

Preclinical findings provide strong evidence for moving vaccine candidate forward in first-of-its-kind study

institution logos

A vaccine against Zika virus is safe and effective when administered both before and during pregnancy, according to new research published in npj Vaccines.

The purified, inactivated Zika vaccine (ZPIV) candidate, developed by Walter Reed Army Institute of Research (WRAIR), is being evaluated in animal models at Texas Biomedical Research Institute (Texas Biomed) in collaboration with WRAIR and Trudeau Institute in New York.

The vaccine candidate has previously been shown to effectively block prenatal Zika virus transmission when given to nonhuman primates prior to pregnancy. This new study goes a critical step further, studying what happens when the vaccine is administered during pregnancy.

“This is a giant step forward,” says Jean Patterson, Ph.D., Professor Emeritus at Texas Biomed. “We have very strong evidence that this vaccine could protect fetal health during the next Zika outbreak.”

Zika virus is primarily transmitted by mosquitoes. It does not typically cause serious illness in most people; the biggest threat is to pregnant women and developing fetuses. During the 2015-2016 Zika outbreak in the Americas, there was a surge in miscarriages and babies born with extremely small heads and other severe birth defects, collectively called Congenital Zika Syndrome. Zika virus continues to circulate at low levels and has been detected in 89 countries and territories to date.

“Zika virus continues to infect people around the world and present a significant risk to maternal-fetal health,” says Stephen J. Thomas, M.D., an inventor of the ZPIV vaccine and a study collaborator. “Because of this, advancing the development of vaccine candidates and studying different use scenarios is incredibly important.”

vaccine vial
A vial of the Zika virus vaccine developed by a team at Walter Reed Army Institute of Research. Credit: WRAIR

The vaccine candidate has completed Phase 1 clinical trials in humans and was well tolerated and elicited an immune response. But clinical trials usually exclude pregnant people, leaving key questions unanswered about whether vaccination during pregnancy would be safe and potent. This new study is believed to be the first to evaluate a Zika vaccine during pregnancy in nonhuman primates. Marmosets, a small nonhuman primate that typically has twins and triplets, are sensitive to Zika virus infection and closely mirror what happens in pregnant humans.

Given the drastic changes that the immune system undergoes during pregnancy, the researchers were not sure if the vaccine, when given during early pregnancy, would generate a protective immune response, such as creating protective antibodies.

“The antibody response when given during pregnancy was similar to the level we observed when administered before pregnancy,” says In-Jeong Kim, Ph.D., a principal investigator at Trudeau Institute. “That is very exciting.”

The vaccine candidate prevented placental damage and sufficiently blocked transmission of Zika virus from mother to fetus. The viral load in placentas and fetuses was significantly lower in the vaccinated group versus the unvaccinated group. Growth and development of fetuses of vaccinated adult marmosets exposed to Zika virus were similar to controls not exposed to the virus. No adverse effects were detected.

What remains to be studied is if protection will last throughout pregnancy and whether offspring born from vaccinated females challenged with the virus during pregnancy are free of Congenital Zika Syndrome. 

“We hope to garner more interest and funding to pursue those next steps,” says Dr. Patterson.