How COVID-19 hybrid immunity could be a potential pandemic game-changer

With the FDA gearing up to decide if all Americans need booster shots, some researchers are pointing to preliminary data suggesting that mixing different vaccines could offer an even stronger immune boost.

For now, data is too sparse to support a mix-and-match strategy, experts say. But scientists are learning more about just how strong the immune response can be for someone who has previously been infected with COVID-19 then gets the vaccine -- a phenomenon called "hybrid immunity."

"The best thing we can hope for is that three vaccine doses will emulate the super immune response, found among those previously infected with the virus," said Dr. Paul Goepfert, an infectious disease physician and director of the Alabama Vaccine Research Clinic. "This [type of immunity] will protect against variants in the future."

With the nation still slogging through the pandemic and contending with the delta variant’s threat of breakthrough infections, "super immunity" becomes an appealing concept.

In one review recently published in Science, people with that hybrid immunity see an immediate and "striking" improvement in protection -- up to a 100-fold increase in their antibody response as compared to what they built up after their COVID-19 infection -- Dr. Shane Crotty, review author and virologist at the La Jolla Institute for Immunology, said.

Experts are also discovering these hybrid antibodies appear to be more versatile and recognize more variants, including those as distant as the original SARS virus, Crotty said.

One yet to be peer reviewed study of previously COVID-19 positive patients who were then vaccinated at least six months later found participants were able to fight off both variants of concern tested: delta, the most infectious, and beta, the most lethal.

"With prior infection, their antibodies are able to recognize numerous variants, but with the addition of the vaccine, they are able to generate a large number to have a stronger effect against the virus," Crotty said.

Like an exercise regimen that pairs weight lifting with cardio, Crotty explained that these individuals benefit from the combination of quantity and varied quality of the immune response they build. And that could indicate promising signs for boosters.

Scientists are seeking to replicate that strong protection, but without people having to contract COVID-19, as it’s universally agreed that infection is not an optimal immunization course.

Instead, they’re hoping booster doses of vaccines could convey a similar effect.

But timing is key when it comes to additional doses, whichever vaccine is given. Researchers say that exact right interval when immune response has matured -- but before protection begins to wane -- is the ideal target.

"Our immune system is built to have repeated exposures to the same antigen," which will "substantially" enhance immune protection, Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center said.

Experts are still gleaning what exactly is the benefit of this enhanced immunity, though it’s not novel to coronavirus.

Flu vaccines, for example, are “boosted" for children receiving them, while adults receive one dose, yearly.

"This is because of hybrid immunity. Adults have already been exposed to influenza and have primed their immune response," Goepfert said.

"What we have seen is that waiting six months does mount a better immune response later," he added. "It seems that our immune system likes to rest and develop antibodies, and then mount a stronger response when it sees the same pathogen again later on."

There is not enough data yet to say if the mix-and-match approach of priming one vaccine and boosting with another is going to offer better or more durable protection. But while the jury remains out, experts are hopeful.

"The mix-and-match approach in vaccine administration has been studied for decades, but unfortunately not for COVID," Barouch said. "while larger studies are underway, it is best to stay with the same vaccine for the booster, if approved."

Lily Nedda Dastmalchi, D.O., M.A., is a physician and cardiology fellow at Temple University Hospital, and a contributor to the ABC News Medical Unit.