Researchers hunt for clues in our blood to discover COVID-19 vaccines of the future

Although front-runner COVID-19 vaccines from Pfizer and Moderna boast efficacy rates of greater than 90%, scientists say it is crucial to continue to study new vaccines, which could be even better than the first-generation shots.

As these vaccines near the finish line, scientists will face a predicament: Successful authorization of the first vaccines will make it difficult, if not impossible, to continue to study COVID-19 vaccines of the future.

Now, a group of researchers say they are zeroing in on a possible solution. By studying monkeys, they say they've identified a clue in our immune systems -- a signature that could show if a vaccine is working. If their results pan out in humans, the findings could help researchers side-step the need for massive, phase 3, placebo-controlled clinical trials, like the ones that are being conducted today for the current COVID-19 vaccines.

Under the lead of Dr. Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, a team of scientists have found that for monkeys given a specific set of antibodies, those antibodies alone can protect them from future infection. Moreover, the amount of those antibodies required for full protection is relatively low. The results were published Friday in the scientific journal Nature.

Since the start of the pandemic, scientists have been racing to identify a signal that can be used to assess whether a vaccine is working. Now, Barouch feels relatively confident that these antibodies -- proteins produced in response to infection -- could be that signal.

Barouch and colleagues demonstrated this by giving COVID-19 antibodies to monkeys who had never before been infected, then exposing them to the virus. They did this to isolate the effect of those antibodies compared to other parts of the immune system.

If Barouch's data in monkeys holds up in humans, doctors in the very near future can use a simple blood draw to reliably determine if a recently vaccinated person is indeed protected. Right now -- because so little is known about this novel virus -- researchers are relying on massive clinical trials comprised of tens of thousands of people, half of whom get a placebo shot, to determine if a vaccine is working.

But these blood tests -- used as a vaccine efficacy litmus test -- are already widely used in clinical practice for diseases like the chicken pox and hepatitis B.

Barouch's findings "are cutting on the heels of good prior data that these [monkey] models do translate well into humans," said Dr. Paul Goepfert, professor of medicine at the University of Alabama at Birmingham and an expert in vaccine design.

The virus used in Barouch's monkey research is nearly "the same virus as in the pandemic," said Goepfert, who was not involved in the study.

These findings also come at a critical time as the first round of vaccines are just about to be authorized by the Food and Drug Administration -- welcome news that could paradoxically jeopardize scientists' quest to develop new and even better vaccines.

"After vaccines become widely available to the public, it will be very difficult to perform placebo studies both from an ethical perspective and also from a practical perspective," said Barouch.

Once we have a vaccine that is approved, it will be ethically unacceptable to continue to test future vaccines against fake injections known as placebos. But scientists argue that we must continue developing new vaccines to make them safer, more effective and longer lasting than the first ones.

To do that, scientists will first need to find an easier way to conduct experiments -- a process that will hinge on finding a well-defined and easy-to-obtain proxy for vaccine protection -- typically from a blood test. Scientists call this proxy an "immune correlate."

"Moving forward, vaccines will have to be licensed based on immune correlates if such a correlate exists," Barouch said. His studies hint that such a correlate does indeed exist, and they could help chart a path forward for future vaccine trials.

This discovery of a sign that vaccines are working will also help save valuable time in the span of weeks, months or even years as their identification will help bypass the large, phase 3 randomized clinical trials currently used to test the vaccines for efficacy.

Researchers also found that the T cell branch of immunity is an important player in protection against COVID-19, yet another finding that Barouch said is further "insight into the immune mechanism of protection against the virus and can be useful for the development of future vaccines as well as public health strategies."

These findings were studied in a small number of monkeys, each group consisting mostly under 10 total, and were assessed in the span of days to weeks.

But according to Goepfert, scientists are now zeroing in on that important goal of a so-called "antibody titer" -- and will soon be able to test patients' blood to see if they are protected months, even a year, after vaccination.

"This is hopeful," Goepfert said.

Shiela Beroukhim Afrahimi, M.D., is an internal medicine resident at Harbor-UCLA Medical Center in Torrance, California, and a contributor to the ABC News Medical Unit.