COVID-19 virus illustration above hand framing sunlight in the sky

The Virus and Vaccines

During the novel coronavirus global pandemic, the Tulane National Primate Research center goes all out to combat COVID-19, an infectious disease like no other.

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Portraits by Paula Burch-Celentano and Sally Asher

For most of us, the novel coronavirus began as a whisper. News of a deadly virus slowly seeped into our national consciousness in much the same way that SARS and MERS had several years prior — murmurings of something awful happening “over there,” an international public health crisis that we viewed more as concerned spectators than participants.

But viruses in general and SARS-CoV-2 in particular don’t care much about borders. Less than a year later, the disease that it causes, COVID-19, has taken an unimaginable toll and the lives of millions around the globe, including more than 245,000 Americans. As the world anxiously awaits a vaccine for COVID-19, we have gained a new respect for the immense power of emerging infectious diseases that can shutter schools, devastate economies, and take countless lives in just a few short months. And we have gained a new appreciation for those who spend their lives studying them, knowing that perhaps they alone can get us to the other side of the biggest public health crisis of our lifetimes. 

The morning after Mardi Gras, Carnival- weary employees streamed their way into the Tulane National Primate Research Center. For several weeks, things had been different. Camera crews strode around the center, mics angled toward prominent researchers who normally toil behind closed doors, immersed in their work. A few weeks prior, the center had announced that it would be among the first research institutions to receive samples of SARS-CoV-2. Now the first vials had arrived, propagated from patient zero — a Seattle man who had contracted the disease while visiting family in China. As a result, the surrounding community of Covington was on edge, wondering how the virus that was wreaking havoc across the globe could be contained within the confines of these buildings. 

Jay Rappaport standing in front of the Tulane National Primate Research Center
Jay Rappaport, director of the Tulane National Primate Research Center

“We have the rare combination of emerging infectious disease expertise and resources here to help respond to this global crisis and with the support of the university, we dove in headfirst.”

Jay Rappaport, director of the Tulane National Primate Research Center

Built to Study Emerging Pathogens

In truth, though, there may have been no better place to receive it. The center, situated in the piney woods north of Lake Pontchartrain, has been quietly working on infectious diseases since the early 1960s and already had world-class scientists at the ready. Its sprawling Regional Biocontainment Laboratory, part of the national biodefense system, is one of a few specifically built to study high-consequence emerging pathogens like SARS-CoV-2. Its highly specialized facilities allow for the study of more animals at a high level of biocontainment than any other place in the country. 

Center Director Jay Rappaport recognized that the center was uniquely poised to respond and moved quickly. 

“We have the rare combination of emerging infectious disease expertise and resources here to help respond to this global crisis and with the support of the university, we dove in headfirst,” said Rappaport.

As reports of the novel coronavirus swept through China and Europe, Rappaport and his team began self-funded pilot studies to develop an animal model of COVID-19. A good animal model faithfully reproduces disease in the way that mimics how humans experience it — a particularly difficult task for COVID-19, considering the vast range of human and animal responses to the virus. But the ability to analyze what makes two individuals respond so differently to the virus can help scientists tease apart why some people experience few symptoms and others, a runaway immune response that leads to organ failure and death. 

Before the human population can receive vaccines or therapeutics for COVID-19, the safety and effectiveness of these products must first be tested in animals, which is only possible if the animal has a response comparable to humans. Nonhuman primates, like the widely used rhesus monkey, often make ideal candidates for disease models due to their physiological similarity to humans and because so much is already known about their immune systems. 

Skip Bohm stands outside the Tulane National Primate Research Center
Skip Bohm, associate director and chief veterinary medical officer

“The rapidity with which progress is being made is astounding, and the work that has been done during this time has been some of the most intense and gratifying of my career.”

Skip Bohm, associate director and chief veterinary medical officer

All Necessary Resources

In early spring, the center paused non-COVID-19 research, redirecting all necessary resources toward COVID-19 vaccine and therapeutic efforts deemed priority by the National Institutes of Health, which oversees the seven National Primate Research Centers. This has required the centers to work more closely together than ever before — stretching and prioritizing resources according to necessity, rapidly sharing data to minimize the use of animals, and harmonizing protocols to ensure reproducibility. Instead of keeping early results close to the vest, as is most often the case in the highly competitive world of research, information is shared and learned in real-time.

Under normal circumstances, significant discoveries are released to the scientific community only upon peer review and publication in academic journals. It is a time-honored, laborious and deliberately slow process to ensure that results are replicable — meaning that what is seen in one lab can be reproduced in another. But during a pandemic, time is a scarce resource. This new way of collaborating advances preclinical work that would normally take upward of five years into less than one. And all of this must happen before these vaccines or treatments can safely be used in humans. 

“We’ve never seen so much open sharing and coordination among entities that are often seen as competing,” said Rappaport. “While this has been a stressful time for everyone, it has also been very encouraging to be a part of this all-hands-on-deck approach.”

Center Associate Director and Chief Veterinary Medical Officer Dr. Skip Bohm oversees the veterinary aspects of research at the center and plays a key role in coordinating veterinary protocols between different entities as part of this harmonization effort. He stresses that while no corners have been cut to move this work forward as quickly as possible, processes have been expedited and those involved have been working longer hours — including nights and weekends — for several months on end. 

And yet for many involved in this work, the extraordinarily long hours and rigorous schedule involved in getting us to the other side of the pandemic bring a sense of pride and purpose. For Bohm, the profound challenges of the pandemic have been balanced by an opportunity to serve and contribute to real solutions. 

“The rapidity with which progress is being made is astounding, and the work that has been done during this time has been some of the most intense and gratifying of my career. I am thankful in these times to have a job that allows me to help,” said Bohm. 

Angie Birnbaum stands outside
Angie Birnbaum, director of biosafety and biocontainment

“We’ve created a highly efficient way to advance this preclinical work quickly by creating a core team of individuals that can get it done right here. Our capacity is huge — but so is our talent and proficiency.”

Angie Birnbaum, director of biosafety and biocontainment

Quality Assurances

As an emerging pathogen, SARS-CoV-2 is highly regulated, and animal research involving it must take place in ABSL-3, or animal biosafety level-3 laboratories. These highly specialized facilities are essential for the testing of potential treatments or vaccines against COVID-19, but there are only a handful of them in the country. The Regional Biocontainment Laboratory at the center, built in the aftermath of 9/11 to bolster our national biodefense system, has both an unusually high capacity for handling this type of work and a team of highly skilled biosafety professionals that can safely get it done. 

As a result, pharmaceutical and biotech companies needing to conduct preclinical trials for their products contacted the center nonstop in the early days of the pandemic, booking the facility’s calendar solid for the next six months. This work, in conjunction with the research deemed priority by the NIH, has kept the facility humming at full capacity. 

Tulane Director of Biosafety and Center Director of Biocontainment Angie Birnbaum leads the team of biosafety professionals at the center who ensure that all of this work runs like clockwork. The quality assurance protocols that Birnbaum established at the center have been standardized for use at other centers, and in leading by example, Birnbaum and her team have established one of the largest, most productive COVID-19 research programs in the country. 

“We’ve created a highly efficient way to advance this preclinical work quickly by creating a core team of individuals that can get it done right here,” said Birnbaum. “Our capacity is huge — but so is our talent and proficiency.”

Birnbaum said that the experience of managing this work in the context of a global pandemic has made her more flexible in her thinking.

“No one who works in this program feels like they are punching a clock when they come to work,” said Birnbaum. “We are thinking outside the box and becoming problem solvers.”

Resources once taken for granted, like the availability of personal protective equipment, now need to be carefully rationed. Staff working long hours now have children stuck at home with distance learning, and instead of being solely concerned with the live virus in the biocontainment laboratories where there are ample safeguards in place, there is now the concern of exposure outside the lab, where the virus is lurking in the community. Birnbaum credits her team as incredible professionals who make immense personal sacrifices to ensure that no matter what, the work continues on schedule. 

“The university has been a leader in this research, and we should all be proud of the amount of work being done at the center that is at a level and pace that neither the staff nor scientists have experienced before,” she said. 

Fast Grants For More Covid-19 Research

For Monica Vaccari, an Italian-born immunologist, reports from her family in Northern Italy about the virus’s impact on the region last spring hit home. Using her expertise in host-immune responses to pathogens, Vaccari received a Fast Grant to contribute to understanding of early-host-immune responses to SARS-CoV-2. 

There is a huge variation in the range of disease that people infected with SARS-CoV-2 experience, from asymptomatic infection to death, and Vaccari hopes to learn what happens in the early stages of infection that determines how individual immune systems may respond. 

Left to right: Monica Vaccari, Tracy Fischer and Mairi Noverr
Left to right: Monica Vaccari, Tracy Fischer and Mairi Noverr

Tracy Fischer has long studied persistent inflammation in the brain due to HIV/AIDS and seeks to investigate what lasting neurological damage might result from COVID-19, a disease that causes a cascade of inflammatory responses throughout the body. 

According to Fischer, understanding how COVID-19 contributes to neurological disease is needed for appropriate treatment of infected patients, as well as for relevant follow-up care after recovery. She received a Fast Grant to investigate the major organ systems implicated in COVID-19 in a nonhuman primate model, which has led to a subsequent investigation on the disease’s long-term effect on brain tissue, particularly in the absence of severe disease.

Mairi Noverr’s research focuses on how the administration of some live attenuated vaccines, like measles-mumps-rubella, can create anti-inflammatory immune responses in nonhuman primates that protect against possible sepsis or death from severe fungal infections. When she saw reports about severe inflammation and septic shock that often precede death from COVID-19, she realized that there was incredible overlap. 

Sitting on what she thought was an essential piece of information that might provide people with an additional layer of protection, Noverr applied and received a Fast Grant award to investigate the idea of using specific vaccine boosters for prevention as a way to activate that anti-inflammatory response. “You want to be able to help in whatever way you can, and this was a way that I could contribute to helping people avoid some of the worst outcomes in a low-risk, high-impact way.”

Fast Grants are unusual in their speed — as they are awarded within 48 hours of application in order to get funding to researchers as quickly as possible. The grants are funded through the Mercatus Center at George Mason University. Fast Grants are modeled after the work of the National Defense Research Committee, an organization that provided quick funding for scientific discoveries and technological developments during World War II.
 

 

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