Is your COVID-19 vaccine working? The future of immunity tests

With troubling evidence that COVID-19 vaccines lose their effectiveness over time, Americans are wondering: Is my shot still doing its job?

Today’s commercially available tests can’t tell you. But a new generation of more innovative tests is on the horizon, promising to provide a more reliable prediction of immunity — and reduce the risk of breakthrough infections.

“We’re getting there,” said UC San Francisco infectious disease expert Dr. Peter Chin-Hong. “I would love to have a test that reassures me, and my patients, that they’re still having ongoing protection.”

Now in development, these future tests could more easily and accurately tell high-risk people — such as frail nursing home residents or the immunocompromised — whether their immune systems responded to the vaccine.

In healthy people, the test could indicate when it’s time for a booster.

“While the third dose undoubtedly amps up antibody levels, it is still unclear as to how long that increase lasts,” said Dr. David Seftel of South San Francisco’s Enable Biosciences, a biotech company spun out of UC Berkeley and Stanford that is designing a new and improved antibody detection test. The company’s ultrasensitive test, which analyzes a finger-pricked spot of dried blood that is mailed to the lab, would be ordered by doctors.

SOUTH SAN FRANCISCO, CA – November 05: Enable Biosciences co-founder and CEO David Seftel poses for a portrait at Enable Biosciences in South San Francisco, Calif., on Friday, Nov. 5, 2021. (Dai Sugano/Bay Area News Group)

“As we return to schools, colleges and the workplace,” he said, “how can we do this with the greatest confidence?”

At Stanford University, research is underway on a different type of test that doesn’t count antibodies but instead looks at the genetic changes that happen in white blood cells promptly after a shot — predicting, within days of vaccination, the vigor of your future immune response.

“The ability to predict the protective immune response to vaccination would be transformative,” said immunologist Dr. Bali Pulendran of Stanford University School of Medicine. His team’s test is based on a new understanding of the genes that are turned “on” or “off” after vaccination. This pattern, a so-called “molecular signature,” could forecast your personal level of protection.https://e10477a655e805c4b86a0039a2eaabfc.safeframe.googlesyndication.com/safeframe/1-0-38/html/container.html

“People want to know whether they would still be protected in six months, one year or two years after they get the vaccine,” he said. “Right now, the only approach is: wait and see.”

At UCSF, a team led by Colin Zamecnik and Dr. Jayant Rajan has created an innovative new blood test called ReScan that reveals individuals’ different antibody responses. It also identifies exactly which parts of the virus are being most strongly targeted by a person’s immune system. Also at UCSF, the lab of Jim Wells, a Chan Zuckerberg Biohub investigator, has created a luminescent biosensor to measure vaccine efficacy.

Currently, the market is flooded with dozens of COVID-19 antibody tests of unknown accuracy and inflated claims. They measure the presence of antibodies that indicate whether or not you’ve been previously infected or vaccinated. Most offer a simple yes-or-no answer.

“They don’t give you the most accurate information as to whether or not you are resistant to reinfection,” said chemist Peter Robinson, co-founder and chief operating officer of Enable Biosciences.

The Food and Drug Administration does not currently recommend that consumers use these antibody tests to assess immunity.

Much better tests are available in clinical research settings. That’s how vaccine manufacturers know that their products are working. But these research-grade tests are technically challenging. They’re not cheap, fast and practical enough for routine commercial use.

Commercial antibody tests have long been available for other diseases, such as hepatitis, mumps, measles and whooping cough.

The challenge is that we’re still learning what level of immune response is needed for protection against COVID-19, said scientists. While we know that higher levels of antibodies prevent hospitalization and death, we don’t yet know exactly how many are needed to protect from infection.

SOUTH SAN FRANCISCO, CA – November 05: Specimen samples sit on the table at Enable Biosciences before being tested for the COVID-19 antibody levels on Nov. 5, 2021, in South San Francisco, Calif. (Dai Sugano/Bay Area News Group)

But the science is improving. For instance, we’ve identified a general threshold of protection – and these new quantitative tests could reveal when antibodies fall below it. It’s also taken time for the technology to evolve, said experts.

The FDA has already authorized one neutralizing antibody test, made by the New Jersey company GenScript. Enable Biosciences plans to submit its application within the next several weeks. 

To be sure, these tests don’t provide the full picture. For instance, they don’t measure the role of the other arm of our immune system, involving memory B cells and T cells. (Those tests are more technically challenging than antibody tests.)

But better tests could greatly improve our clinical care, said Chin-Hong. Perhaps they discover that you have a strong defense, so no booster is needed — welcomed news if you suffered a bad reaction to the initial shot. Or they might reveal that you have a weak defense, so need a fourth, fifth or sixth shot, he said. If they find that your vaccine provided no protection, you’d be offered infusions of monoclonal antibodies.

“The ability of tests to address this in a very quantitative and visible way — that’s very, very powerful,” said Seftel. “This is actionable data.

“It’s fine to get the vaccine, but if it doesn’t work for you, then it’s a problem,” he said. “It’s a problem for you, and it’s a problem for the community.”

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