Doctors in Southern California are working with researchers in Arizona to better understand the body’s sometimes bizarre immune response to COVID-19 — an antibody onslaught that may kill the patient, rather than kill the virus.
The nonprofit Translational Genomics Research Institute (TGen), an affiliate of City of Hope, is peering into specific proteins on the virus to see how they react with different antibodies — a “high-resolution view” that might guide treatment, testing and vaccine development.
“The hypothesis is that antibodies can make things worse, and that’s what’s killing some people,” said John Altin, assistant professor in TGen’s infectious-disease branch. “We want to understand how that might be different from an immune response that protects somebody.”
As many critically ill patients are treated in clinical trials with convalescent plasma therapy — that is, injecting antibodies from recovered COVID-19 patients into those who are very ill, in hopes of triggering protective immune responses — it’s imperative to understand what’s behind the differing reactions.
“Usually, antibodies provide protection, but there may be a bit of an exception with this virus,” Altin said. “That is a serious concern.”
To that end, TGen and the Center for Gene Therapy at City of Hope are cooperating on a COVID Immunity Study that aims to collect blood from COVID-19 survivors.
“The researchers will analyze your blood and profile your immune memory,” the study consent form explains.
Participants can use the TGen kit at home. They’ll get a study kit by mail and collect one small “spot” blood sample, via a finger-prick device, for two consecutive weeks. Then they’ll mail the study kit back to TGen.
About 500 people are expected to participate through the course of the study, and researchers may reach out for additional samples, and/or with additional questions, to see how “immune memory” changes over time.
Participants must be U.S. residents, at least 18 years old, have tested positive for COVID-19, and then recovered. For more information, see https://covidimmunity.org/.
“This will help us learn more about how, when and why we produce antibodies in response to a COVID-19 infection,” said David Engelthaler, director of TGen North, in a prepared statement. “One class of antibodies tackles the infection first, and then another comes in to finish the job. Knowing when these different immune responses occur, and how long they last, could help us understand if some patients gain a certain degree of immunity against reinfection. We need to know how that works.”
How’s this study different?
While large-scale clinical trials involving convalescent plasma are under way all over the nation, this study aims not to treat the disease, but to better understand the mechanisms behind it.
TGen describes its approach as “a high-resolution view” of the antibody response. It seeks to not only map the virus’s proteins in detail, but to also see which parts of those proteins are targeted by antibodies.
“Our approach will not only tell you which proteins are being targeted, but also be able to tell which regions of each protein are being targeted,” Altin said in a statement. “Each protein can be recognized by many different types of antibodies. By looking at this level of detail, we then could see elements of the antibody response that others might be missing.”
TGen hopes to tease out subtle differences that can help develop therapies, vaccines and better antibody testing.
“Others are looking at responses to the entire protein. Our approach is a little different. When we look at the antibody response, we divide it up into thousands of pieces. There’s potential for that to tell us what a beneficial and un-beneficial response might look like,” Altin said.
John Zaia, director of the Center for Gene Therapy at City of Hope, is working with TGen, and has other COVID-19-related projects happening as well.
Zaia is leading a research project at City of Hope, in collaboration with Altin’s lab, that could lead to development of a COVID-19 virus antibody neutralization test, which would quantify antibodies.
Zaia also has received a $750,000 grant from the California Institute for Regenerative Medicine for a clinical study on the use of blood plasma as a potential treatment for COVID-19.
“They’re doing what you could call qualitative and quantitative measurements of the nature of the antibody — what does it actually bind to?” Zaia said. “The virus has this surface protein, the spike protein, but there are also other things the immune system might be seeing. It might be focused on one or more parts of the spike.”
The CIRM project will focus on finding plasma donors to determine if there’s any correlation between the outcome in the sick patient who received the plasma and the specific antibody that went in. It will focus on under-served areas.
Duarte-based City of Hope was founded in 1913 and is a founding member of the National Comprehensive Cancer Network. It has many sites throughout Southern California, and is investing $1 billion to establish clinics and a cancer center in Orange County. A clinic opened in Newport Beach in January, and a hospital dedicated to cancer research is slated for Irvine.
On the forefront of science, new discoveries are made every day and so much is still unknown.
“I think the FDA said it best: There’s no way that one group could solve all the problems, do all the testing that needs to be done,” Zaia said. “The whole field is so new.”
There’s a balance that must be struck between moving quickly and moving carefully, Aiten said. “We should know a lot in the next three months about how the antibody response looks,” he said. “Vaccine development will take much longer.