AMR Knoxville in respiratory syncytial virus vaccine clinical trials
When disease strikes a community, it’s easy to feel helpless. But amid a new wave of RSV in Tennessee, older adults take an extraordinary step to stop it.
A Knoxville clinical trial could lead to the approval of a vaccine decades in the making.
Research company AMR Knoxville is taking part in vaccine clinical trials for respiratory syncytial virus, commonly known as RSV, for adults. RSV is a highly contagious, seasonal respiratory disease that primarily afflicts older adults and young children.
Older adults in Knoxville can help make it happen. The company is enrolling volunteers now.
RSV test positivity rates began to climb across Tennessee between mid-May and June. The disease is usually quiet this time of year, but test positivity rates peaked at 35% in mid-June, almost as if it was the normal wintertime infection season.
While RSV’s off-season spike made headlines this summer, the vaccine study has been in the works for quite a while. For 18 months, a new phase 3 clinical trial will track the health of 300 to 400 local adults who are 60 and older.
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The local study, which should be finished in early 2024, could be a final piece of the puzzle before FDA approval. If the trial is successful, it would take a minimum of three more years to bring the yet-to-be-named vaccine to market.
“There has been interest in developing an effective vaccine against RSV for several years,” Dr. Bill Smith, the local study lead from AMR Knoxville, told Knox News. “It represents a significant health problem, not just in children but in older adults.”
Finding purpose in fighting the disease
For Smith, an East Tennessee native, fighting RSV is personal.
“My sister-in-law died of RSV at age 61, just a few years ago,” Smith said. “It makes it more personal. I have a real interest in seeing RSV have some effective vaccine.”
Smith has been conducting clinical trials since 1985. His father was a family physician in Tazewell for decades. Smith worked in New Orleans for years but returned to East Tennessee after the devastation of Hurricane Katrina. He maintains clinical research sites in both cities.
In 1994, Smith helped found the Alliance for Multispecialty Research, a network of clinical research sites that has grown to 14 research clinics across nine states. During the pandemic, AMR was part of the race to develop a COVID-19 vaccine.
“We did Moderna. We did Pfizer. We did J&J. We did AstraZeneca. We did Merck,” Smith said. “We had well over one thousand people that were in our coronavirus vaccine studies that were able to get vaccinated before the vaccines were available.”
RSV is elusive
Approximately 14,000 Americans over 60 die annually from RSV infections.
A study in the New England Journal of Medicine showed that RSV caused comparable rates of hospitalization to seasonal influenza in older adults. Outbreaks of RSV in nursing homes and long-term care centers are common and deadly.
Scientists have been trying to develop a vaccine against RSV for 60 years. Traditional vaccination methods, like using dead or attenuated RSV as the main ingredient of the vaccine, have been unsuccessful.
In the 1960s, for example, a pediatric RSV vaccine using formalin-killed virus was tested in children. Instead of producing a protective response, the dead virus triggered a generalized, non-protective inflammatory response. Many children wound up hospitalized and two died.
It took decades of research to find out how this happened, in part because RSV is an evasive virus, even when it’s not active.
Most RSV surface proteins don’t produce strong immune responses and the virus has evolved several mechanisms to escape detection from the immune system. It can force infected cells to release decoy proteins, sending immune cells on a wild goose chase.
Developed by Janssen, which is Johnson & Johnson’s vaccine division, the RSV vaccine being tested in Knoxville uses the same technology as the single-shot Johnson & Johnson COVID-19 vaccine. It exposes the immune system to a simulated infection, targeting a critical binding protein for RSV in this case instead of COVID-19.
It’s one of many experimental vaccines that has been developed over the decades. Today, there are several competing vaccines at different phases of clinical trial. Moderna, for example, has an mRNA RSV vaccine in phase 1 clinical trials.
As a stage 3 clinical trial, the initial safety and efficacy tests have already been completed. In early studies, the vaccine was shown to be protective without any major side effects.
Its phase 2 clinical study showed that the vaccine could be safely introduced alongside a seasonal flu vaccine to add protection from both diseases without adverse effects.
It isn’t yet known whether immunity from this new RSV vaccine lasts for multiple years. This trial will help determine that.
The local AMR study is just one portion of complex trial, which has 23,000 participants worldwide.
What is RSV?
RSV primarily infects the cells that line the interior of the lung, causing them to die and shed into the airway.
It is estimated to cause approximately 3.4 million hospitalizations and roughly 100,000 deaths worldwide in children under five. RSV is thought to be the second-most significant seasonal respiratory infection after flu.
Almost all children get infected by RSV by age two, but the vast majority of infections are mild and easily mistaken for colds. Children and adults can get infected by RSV repeatedly and it’s typically mistaken for colds or allergies.
“If your kid comes home from day care and they have a cold, it’s like, this is one of the million colds that my kid has,” said Tim Sparer, professor of virology at the University of Tennessee at Knoxville. “It isn’t until it gets worse, your kid is having trouble breathing, that you take them in and it’s like ‘Oh this is RSV.'”
East Tennessee Children’s Hospital started to see increased RSV hospitalizations this summer.
In older adults, RSV causes coughing, pneumonia and fever. It can exacerbate COPD or congestive heart failure and can lead to a downgraded quality of life.
Early RSV symptoms in adults are harder to distinguish from colds or other respiratory infections. Researchers believe that many older adults go misdiagnosed or undiagnosed for serious RSV. Even viral tests frequently yield false negatives in older adults.
“This leads to great difficulty in ascertainment of RSV as the original cause of deteriorating health in frail elderly persons,” wrote one research team in the British Medical Journal.
People 60 years and older who are in relatively good health are eligible to participate in the Knoxville study.
Volunteers will get routine checkups and track their symptoms on a smartphone app. The study is designed to watch patients over two winters, when RSV and other respiratory viruses typically flourish.
“This is a surveillance study,” Smith said. “When people experience symptoms consistent with flu they come in and we do testing for flu, RSV and COVID to determine which respiratory diseases, if any, are present.”
Volunteers will be paid up to $962 for their time and for tracking their symptoms. AMR also pays for referrals to eligible participants.
“It’s basically payment for their time and hassle,” Smith said. “We recognize that the studies couldn’t happen without their participation so its a way of saying thank you.”
Volunteers can sign up at amrknoxville.com or by calling AMR at 865-305-3784.