‘Super Immunity’ Same Whether COVID or Vaccination Is First



Jan. 27, 2022 — It turns out it’s the combination that counts, not what comes first.

Strong immunity against coronavirus infection is about the same between people who got vaccinated and then had a breakthrough infection vs. others who got infected first and then received immunization, a new study reveals.

Either way, people generally end up with a robust immune response because of this hybrid protection.

“It was interesting that the immune boost for vaccination following natural infection was so uniform, given that natural infection alone produces highly variable immunity,” says study author William B. Messer, MD, PhD.

“This was novel, if not completely surprising,” he says.

The study was published online Tuesday in Science Immunology.

Investigating Immune Responses

Messer; lead author Timothy Bates, a PhD student; and their colleagues studied 104 employees at Oregon Health and Science University who were vaccinated against COVID-19. They divided them into three groups: 42 who were vaccinated but never had COVID-19, 31 who developed the illness and later got vaccinated, and 31 others who had a breakthrough infection.

Ninety-six participants received the Pfizer vaccine, six received Moderna, and two received the Johnson & Johnson vaccine.

Researchers compared immune reactions to coronavirus variants using blood samples in a laboratory. The research was done before the emergence of the Omicron variant, although the investigators believe the findings still apply.

Average antibody levels were 3.6 times higher in hybrid immune groups, compared to the vaccination group alone, a significant difference. At the same time, average levels were 2.5 times higher in the breakthrough group.

But investigators found no significant difference between the hybrid and vaccination group antibody responses.

“Prior infection is a ticket to enhancing your immune response to vaccination, giving more potent immunity than vaccine alone,” says Messer, an associate professor of molecular microbiology and immunology at Oregon Health and Science University.

In addition, “Our work shows … the breakthrough infection will result in an immune response more likely to protect against further breakthrough infections.”

Unlike vaccination alone, age was not a significant factor in hybrid immune reactions. In other words, older people were just as likely to mount “super immunity” as younger participants.

‘Natural Immunity’ Term Contentious

There has been some controversy around the term “natural immunity,” particularly in politically charged discussions in the United States.

“I think there has been some confusion around natural immunity being somehow equivalent to vaccine-elicited immunity in terms of [being] just as complete or protective,” Messer says.

But prior research shows natural immunity can be more variable, he says, and is more likely to be provide less consistent protection, compared to protection that comes from a vaccine.

Vaccination Remains Essential

Although the hybrid immune response was strong regardless of the order of protections, the authors included a caveat.

“Because vaccination protects against severe disease and death, it is safer for individuals to be vaccinated before rather than after natural infection,” they wrote.

“One big message is that our work shows vaccines still can and should play an important role in protection,” Messer says.

“Vaccination raises all boats — if you have been previously infected or if you experience a breakthrough infection. In both cases, your immunity will be closer to complete.”

Staying the Courses on Omicron

When it comes to Omicron, “the way to be prepared is to be vaccinated, preferably with two doses of mRNA, to avert the serious complications of COVID-19,” said Hana El Sahly, MD, when asked to comment on the study.

“The vaccines continue to be highly effective against severe COVID-19 and death through the viral variants’ permutations, and that is on top of a remarkable safety record in hundreds of millions of persons around the globe,” says El Sahly, a professor of molecular virology and microbiology at Baylor College of Medicine in Houston.


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