What you need to know about ‘original antigenic sin’ with fall COVID boosters around the corner

With new COVID variant-specific boosters set to roll out in the coming week, vaccine scientists say more research is needed to understand how a person’s early immune response – either through vaccination or infection itself – may impact future protection against an ever-evolving virus.

The body learns its best defensive moves when it first encounters a virus, experts say. However, once a virus evolves, the immune system is slower to respond.

This is a phenomenon called “original antigenic sin” or “immune fingerprinting”.

Scientists say that despite living nearly three years amid the pandemic, there are still unanswered questions. For example: What is the best way to maximize protection through vaccination? Which vaccine formulation would provide the broadest immune coverage? How often should people get booster shots?

The answers would help public health authorities decide on future vaccination strategies such as vaccine formulation and when doses are given.

What is original antigenic sin or immunological fingerprinting?

“There’s a theory that our immunological response to first exposure to a virus can somehow imprint your immune system,” said John Brownstein, ABC News contributor and chief innovation officer at Boston Children’s Hospital.

The human immune system’s best playbook is against an invader it already knows, experts say. But the virus continued to change shape, evolving into new variants that are still recognizable, but slightly different from the predecessors.

“In other words, the first antigens you are exposed to [are] the ones your immune system is most trained to recognize and respond to more strongly next time,” said Dr. Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center.

What does this all mean in terms of COVID vaccines and boosters?

Some experts say they fear frequent boosters with the original version of the vaccine may have inadvertently exacerbated the immune imprint. At this point in the pandemic, some adults have received four or more doses of the same vaccine.

Although still theoretical, some scientists worry about a potential backfire, with frequent boosts handcuffing the body’s natural immune system and leaving it exposed to radically different variants that could emerge in the future.

“Where it matters is if you continue to give booster doses with [original] strain, and continue to lock people into this original answer. It then becomes more difficult for them to respond to an essentially completely different virus,” says Dr. Paul Offit, professor of pediatrics at Children’s Hospital of Philadelphia.

Other scientists disagree, saying the immune system is adaptable and dynamic. The boosters, they claim, will not freeze the immune system in place.

Meanwhile, updated boosters are expected to roll out this week. These boosters are specifically designed for the new omicron BA.4 and BA.5 sub-variants.

“When we have an omicron-specific booster, it doesn’t make sense not to use it,” said Dr. Anna Durbin, director of the Johns Hopkins Bloomberg School of Public Health Immunization Research Center. “The omicron spike protein is very, very different from the current vaccine spike protein.”

But even in the face of new variants, studies show that the original booster continued to reduce the risk of serious illness from COVID-19. Fully vaccinated people with at least the primary series were five times less likely to die from COVID in the summer of 2022, according to the Centers for Disease Control and Prevention.

“I think the concern is that if the virus continues to mutate, maybe the [original] the vaccine isn’t going to continue to do well against that, but I suspect we’re still going to do very well against severe illness and hospitalizations,” said Dr. Paul Goepfert, professor of medicine in the Division of Infectious Diseases at the UAB.

The vaccine schedule may also need to be considered as the country moves from original doses to updated boosters.

“It’s true that the best boosts are usually the ones that are given infrequently, that immunologically, if you boost too much and too frequently, you often have a weaker immune response in the end,” Barouch said.

Does this affect the future of the pandemic?

“I don’t really think [immune imprinting] poses a threat,” Durbin said, “I don’t think it’s going to inhibit the ability of the immune system to recognize other variants or to induce immune responses to other variants, either through infection or through vaccines”.

With the virus continually evolving, experts note that continued research is essential to understand how phenomena such as immune fingerprinting might affect the fight against COVID.

“I don’t think it causes a problem, but it’s an important line of research that needs to be investigated,” Brownstein said. “We’re not sure if this concept is actually harmful, or even a benefit for potential future infection risks.”

Youri Benadjaoud and Emma Egan are MPH candidates at Brown University and members of ABC News’ medical unit.

Leave a Comment