While COVID-19 vaccines are dominating coronavirus news, researchers are still working on treatments for the virus as well, and progress in that regard is being made by a team led by UAB scientists.
James J. Kobie, PhD, associate professor in the UAB Department of Medicine Division of Infectious Diseases, Mark R. Walter, PhD, who is a professor in the UAB Department of Microbiology, and Luis Martinez-Sobrido, PhD, a professor at the Texas Biomedical Research Institute, have discovered an inhaled monoclonal antibody treatment that shows therapeutic efficacy. It has been licensed for development to Aridis Pharmaceuticals, Inc.
"The predominant antibody response against SARS-CoV-2 targets the spike protein on the virus, more specifically the receptor-binding domain of the spike protein, which binds to the receptor on human cells referred to as ACE2," Kobie said. "The thought is if you have antibodies that bind to the spike, they would block the ability of the virus to bind to human cells and be able to neutralize the virus."
Walter's team generated custom recombinant SARS-CoV-2 spike proteins that can bind to antibody-producing B-cells. Patients who had recovered from SARS-CoV-2 were screened for high levels of antibodies against the receptor-binding domain in their plasma. "We were able to identify the B cells from these patients, with the thought that the antibodies they produce would be very good at neutralizing the virus, by inhibiting the ability of the virus to attach to human cells using the ACE2 receptor," Kobie said.
After isolating those B-cells and producing the antibodies, they were sent to their virologist colleague, Martinez-Sobrido, in Texas. He tested the antibodies for their ability to inhibit the virus in tissue culture dishes and in hamster animal models.
They discovered that when hamsters were given the antibodies through an injection before they had the virus, the antibodies would eliminate the virus. "Similarly, we can give the antibody six to 12 hours after we've infected the hamsters with virus, and the antibodies still mediate the clearance of the virus," Kobie said.
Aridis Pharmaceuticals is a company with a track record of developing antibodies against infectious diseases and delivering them by inhalation. Their collaboration facilitated the delivery of this antibody treatment.
"The virus is primarily in the respiratory tract," Kobie said. "If you deliver the antibodies directly to the lungs, you get much more efficient uptake. We were able to show that by delivering the antibody directly to the lungs, through inhalation using a nebulizer, we could provide 100-fold less antibody than would be necessary by systemic intravenous delivery."
"In addition, since an IV isn't required, this treatment can be delivered at home or in a nursing home," Walter said. "That's another exciting benefit of this treatment."
The treatment is expected to enter clinical trials in 2021. And while news on the vaccine front is promising, Kobie and Walter emphasized the need to continue working for a treatment as well, since vaccines will not be 100 percent effective, and some individuals may not be vaccinated.
"Our goal is to use this as a therapeutic, primarily for people who are not hospitalized and have a lower disease burden. But there are instances where antibodies can be given as a preventive measure," Kobie said.
Kobie and Walter acknowledged the rest of the team that is responsible for the development of this treatment, including other authors in the study: Michael Piepenbrink, Ashlesha Deshpande, Madhubanti Basu, Sanghita Sarkar, Christopher Bates, Reuben Burch, Nathaniel B. Erdmann and Paul A. Goepfert in the UAB Department of Medicine, Division of Infectious Diseases and Department of Microbiology; Andreas Loos, Jennifer Woo, Phillip Lovalenti, Derek Sloan and Vu L. Truong with Aridis Pharmaceuticals; and Chengjin Ye and Kevin Chiem at theTexas Biomedical Research Institute.
"Mark and I are PhD bench scientists," Kobie said. "I'm fortunate to be in the Infectious Diseases Division which is part of the Department of Medicine. I'm surrounded by great clinician-scientists and their laboratories. It was these clinician-scientists early on being able to identify the patients, collect samples and set up the resources that allowed us to do this research. It was a big collaborative effort between clinicians and bench researchers."
Walter agreed. "The team effort has been meaningful in this difficult time. To be able to do this science together has been great, and we hope that it's beneficial."