Two paths toward ‘super immunity’ to COVID-19

Jan. 27, 2022

A new study from Oregon Health & Science University (OHSU), found that two forms of immunity, breakthrough infections following vaccination or natural infection followed by vaccination, provide roughly equal levels of enhanced immune protection.

“It makes no difference whether you get infected and then vaccinated, or if you get vaccinated and then a breakthrough infection,” said co-senior author Fikadu Tafesse, Ph.D., assistant professor of molecular microbiology and immunology in the OHSU School of Medicine. “In either case, you will get a really, really robust immune response — amazingly high.”

The research follows an OHSU study published in December that described extremely high levels of immune response following breakthrough infections — so-called “super immunity.” That study was the first to use multiple live SARS-CoV-2 variants to measure cross-neutralization of blood serum from breakthrough cases. The study was published in the journal Science Immunology.

They also found that it doesn’t matter whether someone gets a breakthrough infection or gets vaccinated after a natural infection. In both cases, the immune response measured in blood serum revealed antibodies that were equally more abundant and more potent — at least 10 times more potent — than immunity generated by vaccination alone.

One caveat, the study was done before the emergence of the highly transmissible Omicron variant, but researchers expect the hybrid immune responses would be similar.

“The likelihood of getting breakthrough infections is high because there is so much virus around us right now,” Tafesse said. “But we position ourselves better by getting vaccinated. And if the virus comes, we’ll get a milder case and end up with this super immunity.”

They found “hybrid immunity” generated greater levels of immunity compared with people that were vaccinated but with no infection.

“I would expect at this point many vaccinated people are going to wind up with breakthrough infections — and hence a form of hybrid immunity,” said senior co-author Bill Messer, M.D., Ph.D., associate professor of molecular microbiology and immunology, and medicine (infectious diseases) in the OHSU School of Medicine.

Over time, the virus will run into an ever-expanding pool of human immunity.

OHSU scientists say they haven’t tested multiple rounds of natural infection, although many people will likely find themselves in that category, given that millions of people in the United States and around the world remain entirely unvaccinated. With the spread of the highly contagious Omicron variant, many unvaccinated people who were previously infected are likely to confront the virus again.

For that group, previous research reveals a much more variable level of immune response than vaccination, Messer said.

“Immunity from natural infection alone is variable. Some people produce a strong response and others do not,” said Curlin, associate professor of medicine (infectious diseases) in the OHSU School of Medicine and director of OHSU Occupational Health. “But vaccination combined with immunity from infection almost always provides very strong responses.

“These results, together with our previous work, point to a time when SARS-CoV-2 may become a mostly mild endemic infection like a seasonal respiratory tract infection, instead of a worldwide pandemic.”

OHSU release

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