COVID-19 vaccine holdouts have no monopoly on doubt. Even those scientists who believe that the vaccines are the best way to end the pandemic wish they had more evidence.
Proof when and how long the vaccines protect. A booster dose is a better option for an individual. Even proof that one vaccine may work better than the other.
But all those things need something that is not yet established: a common currency through which people’s levels of protection can reliably be measured, valued, and compared. It is a measure of how strong a person’s defenses have become. If it falls, it means they are more vulnerable.
In vaccine terminology, this measure is known as a “correlate to immunity.” Although it’s not proof, it serves as a guide for the search for more evidence.
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The absence of these immune correlates is “one of the struggles we’re all having,” said Dr. Hayley Gans, a pediatric infectious disease specialist at Stanford University and member of an expert panel that advices the Food and Drug Administration on COVID-19 vaccines.
Scientists can take years to come up with a standard method to measure the protection of any vaccine. Dr. Joel I. Ward , is a former professor of immunology at UCLA. Sometimes they give up.
That was the case when a whooping cough, or pertussis, vaccine was introduced in the early 1950s. Over the next 30 years, babies stopped dying of whooping cough, and despite the absence of a correlate of immunity, scientists declared victory. Then in the early 1990s, when doctors began to detect pertussis infections in adolescents and adults who had been vaccinated, scientists shrugged and recommended boosters.
The earliest COVID-19 vaccines began rolling out less than a year ago, so it’s no surprise that scientists have yet to find and agree on a common measure of immunity, Ward said. This may seem like an obscure debate, but scientists could use a method to determine if a vaccine is protecting them.
Among other things, it would allow doctors to assess whose immunity to COVID-19 is slipping and identify those who could benefit from a booster.
An inexpensive, reliable and easy way to determine the ideal correlate of immunity is with a commercial test. Scientists might be able to find a test that accurately captures the immune response protecting the person. This would help them understand how vaccines work.
Scientists will likely settle for a surrogate measure, which could be a protein, process, or waste product that is related to immunity.
The complexity of the immune system makes it all the more difficult. It is multilayered with many divisions of labor, which are not always clearly distinguished. Its many characters, including lymph nodes and white blood cells as well as five classes of antibodies and a variety B and T cells, interact in many ways with one another over time. Moreover, while some actors may look identical at first, they take on new roles as their age.
It might look like a war if you could see the immune system’s reaction to a virus invader and its attempts to escape. The first encounters can be unpredictable, there are skirmishes that are won and lost, reinforcements arrive and the battle lines shift. Sometimes, the war is won in mucus membranes where respiratory viruses first get into. Sometimes, the coup de grace arrives in the bloodstream after an invader has broken through the gates. Taking a picture during this ongoing drama can give a misleading view of where the wars are being waged, how they will end or whether truces that end hostilities will be held.
Finding a single metric that captures all this dynamic complexity is a tall order, said Dr. Archana Chatterjee, a pediatric infectious disease expert at the University of Chicago who serves on the FDA advisory board.
“This doesn’t seem like simple mathematics…it’s calculus,” she stated. Add the unknowns about the coronavirus and humans’ unpredictable behavioral responses to the pandemic, she added, and “it’s three-dimensional chess.”
Many researchers believe antibodies that target the coronavirus’ telltale spikes and another feature called the receptor binding domain could be a good correlate of immunity. Dr. Anthony Fauci ,, who heads the National Institute of Allergy and Infectious Diseases, are some of those who support this idea.
Some antibodies can be trained by infection or vaccine to recognize and neutralize pathogens. Their numbers can increase in the first 24 hours after exposure. They can also be easily detected in the bloodstream.
Although they are proteins that decay, antibodies also degrade over time. The task of ordering replacements is then handed to a group of T cells and B cells, in which immune memory is located. Some of these T cells can also kill infected cells. One preliminary study that found that vaccinated people with no detectable antibodies to COVID-19 in their blood were still about 50% less likely than unvaccinated adults to become severely ill.
Relying on these neutralizing antibodies as the only measure of immunity would be a mistake, said Dr. Paul Offit, a vaccine expert at Children’s Hospital of Philadelphia who serves on the FDA panel. He said that antibodies will eventually decay and that failing to credit the immune system for its other protection mechanisms will make it impossible for us to continue with vaccinations.
“Does anyone really want to get a yearly vaccination? Offit stated, “I hope not.” “I hope not A single measure of immunity could also offer another benefit: it would allow one to assess the “natural immunity” of a person after they have recovered from infection, and then compare that with the protection provided by vaccines. Doctors might find that some people can safely skip a vaccine; alternatively, COVID-19 survivors might realize they still need a dose or two of vaccine for their protection.
The right correlate of immunity could also allow doctors to establish a threshold below which a person (or a group of persons, like those over 65) becomes vulnerable to severe illness. This would warn the patient to avoid infected people and get a booster.
Doctors and patients could use reliable indicators of immunity to help them choose the best boosters. A test that showed people with breakthrough infections had strong immunity would indicate that the coronavirus has evolved to overcome vaccine defenses. It may be necessary to adjust booster doses.
If the vaccine fails to produce strong immune memory, the booster dose may need to be increased or the time between shots extended. Experts believe either vaccine could produce stronger and longer-lasting immune responses.