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Booster dose and breakthrough infection provide similar COVID ‘super immunity,’ study finds

OHSU laboratory research compares immune response to live virus variants, including omicron
A person holding their arm while a medical professional injects them with  vaccine.
Although omicron may cause a less severe illness, it is significantly more transmissible. Getting the COVID-19 vaccine is encouraged and effective, studies show. (Getty Images)

A breakthrough infection or a booster dose provide roughly equally enhanced immune response against the virus that causes COVID-19, according to new laboratory research from Oregon Health & Science University.

Even so, study authors say it pays to get boosted when it comes to gaining so-called “super immunity.”

The reason: One involves infection with a virus that has already killed almost 1 million Americans, while the other relies on a proven vaccine.

The study published this week as a preprint in MedRxiv.

The new findings build on a previous line of laboratory research measuring cross-neutralization of blood serum against the SARS-CoV-2 virus, this time using the highly contagious omicron BA.1 variant that drove a surge in cases worldwide over the winter.

Fikadu Tafesse, Ph.D., smiles outside the Vollum amid the garden greenery.
Fikadu Tafesse, Ph.D. (OHSU)

“The high transmissibility of omicron has led to a massive increase in the number of individuals with combined natural and vaccine-induced immunity,” said co-senior author Fikadu Tafesse, Ph.D., assistant professor of molecular microbiology and immunology in the OHSU School of Medicine. “Ongoing cycles of natural infection and the widespread rollout of booster vaccines suggest that the enhanced immunity observed here will apply to an ever-greater proportion of the world’s population.”

The laboratory findings show the heightened immune response was roughly similar between the breakthrough and boosted groups.

Marcel Curlin, M.D., stands outside Mack Hall at OHSU on a wet spring day.
Marcel Curlin, M.D. (OHSU)

“Some may ask whether it’s a good idea to just get infected and get it over with. We would not recommend ‘getting COVID-19 to avoid getting COVID-19,’ so to speak,” said co-senior author Marcel Curlin, M.D., associate professor of medicine (infectious diseases) and medical director of OHSU Occupational Health. “Boosters provide as much immunity enhancement as natural infection, so the most practical way to protect yourself and those around you who may be more susceptible to severe infection is to get vaccinated.”

Curlin pointed out that while most COVID-19 cases now are mild, the high transmissibility and large number of infections means there will still be a significant number of severe cases and deaths — particularly among those of advanced age or with preexisting conditions.

The study involved a total of 97 people, all OHSU employees who were vaccinated with the Pfizer mRNA vaccine. They were divided into three groups: Those who were vaccinated with the two-dose primary series; those who received a third booster dose; and those who had a breakthrough infection after two doses but not three.

Blood serum from all three groups was exposed to three live virus variants — the original, delta and omicron BA.1. Researchers then measured immune response, in terms of the volume of antibodies generated and the ability of the antibodies to neutralize the live virus. 

Researchers found “significantly increased” immune response with the three-dose and breakthrough groups compared to the two-dose group. This heightened immune response was similar between the boosted and breakthrough groups.

These findings are especially significant as more people develop strong immune responses to COVID-19, either through vaccination alone or a combination of vaccination and natural infection. This widespread immunity will be relevant to future variants — and the world will be increasingly protected from the threat of COVID-19.

The work follows on two previously published studies. The first, published in December 2021, found that breakthrough infections generate enhanced immunity. The other, published Jan. 25, found breakthrough infections and vaccination after natural infection both produced a similarly potent immune response.

The new study compares immunity from breakthroughs to immunity generated by a third booster dose of the Pfizer mRNA vaccine.

In addition to Tafesse and Curlin, co-authors include Timothy Bates, Gaelen Guzman, Devin Schoen, Savannah McBride and Samuel Carpenter.

Funding for the study was supported by the M.J. Murdock Charitable Trust; the OHSU Foundation; the National Institutes of Health training grant T32HL083808; and OHSU Innovative IDEA grant 1018784.

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