Researchers Discover Two Paths Toward “Super Immunity” to COVID-19

OHSU laboratory research compares routes to immunity involving vaccination.

New laboratory research from Oregon Health & Science University reveals more than one path toward robust immunity from COVID-19.

A new study finds that two forms of immunity – breakthrough infections following vaccination or natural infection followed by vaccination – provide roughly equal levels of enhanced immune protection.

The new study will be published online today (January 25, 2022) in the journal Science Immunology.

“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 new study 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.

The study was done before the emergence of the omicron variant, but researchers expect the hybrid immune responses would be similar with the new highly transmissible variant.

“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.”

Researchers recruited a total of 104 people, all OHSU employees who were vaccinated by the Pfizer vaccine, and then carefully divided them into three groups: 42 who were vaccinated with no infection, 31 who were vaccinated after an infection, and 31 who had breakthrough infections following vaccination. Controlling for age, sex and time from vaccination and infection, the researchers drew blood samples from each participant and exposed the samples to three variants of the live SARS-CoV-2 virus in a Biosafety Level 3 lab on OHSU’s Marquam Hill campus.

They found both of the groups with “hybrid immunity” generated greater levels of immunity compared with the group that was vaccinated with no infection.

A path toward endemic COVID

With the wildly contagious omicron variant now circulating across the globe, the new findings suggest each new breakthrough infection potentially brings the pandemic closer to the end.

“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., assistant 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.

“I can guarantee that such immunity will be variable, with some people getting equivalent immunity to vaccination, but most will not,” he said. “And there is no way, short of laboratory testing, to know who gets what immunity. Vaccination makes it much more likely to be assured of a good immune response.”

Senior co-author Marcel Curlin, M.D., agreed.

“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.”

Reference: “Vaccination before or after SARS-CoV-2 infection leads to robust humoral response and antibodies that effectively neutralize variants” by Timothy A. Bates, Savannah K. McBride, Hans C. Leier, Gaelen Guzman, Zoe L. Lyski, Devin Schoen, Bradie Winders, Joon-Yong Lee, David Xthona Lee, William B. Messer, Marcel E. Curlin and Fikadu G. Tafesse, 25 January 2022, Science Immunology.
DOI: 10.1126/sciimmunol.abn8014

In addition to Tafesse, Messer and Curlin, co-authors included Timothy Bates, Savannah McBride, Hans Leier, Gaelen Guzman, Zoe Lyski, Devin Schoen, Bradie Winders, Joon-Yong Lee of the Pacific Northwest National Laboratory and David Xthona Lee.

The study was funded by a grant from the M.J. Murdock Charitable Trust; an unrestricted grant from the OHSU Foundation; the National Institutes of Health, training grant T32HL083808 and grant R01AI145835; and OHSU Innovative IDEA grant 1018784.

The study authors acknowledge the research participants for their generous contributions; OHSU’s COVID-19 serology study team and the OHSU Occupational Health Department for recruitment and sample acquisition; and the OHSU clinical laboratory under the direction of Donna Hansel, M.D., Ph.D., and Xuan Qin, Ph.D., for SARS-CoV-2 testing and reporting.

COVID-19ImmunologyInfectious DiseasesOregon Health & Science UniversityPopularPublic HealthVaccine
Comments ( 12 )
Add Comment
  • Michael Q. Rudnin

    No difference? If you get vaccinated and then get covid, you won’t be hospitalized or die.
    I’d say that’s a big difference.

  • Human

    Meanwhile, 2 years in and still unvaccinated…..exposed daily in a high risk healthcare environment for my job which includes going into Urgent Care Covid positive patient rooms and Covid ICU units. Have to get weekly tested due to approved vaccination exemption. 3 antibody test have come back negative indicating no prior infection. How do you explain that? I’ve been told that there is absolutely no way I would not get infected. Yet here I am. I must be the luckiest person on the Planet!!! and apparently my wife is too as she has never been infected either. WOW we are the luckiest people on the planet!! (sarcasm). But hey it’s the internet..maybe I don’t even exist, you’ll never know will you? Hot tip for those interested: cut out heavily processed prepackaged foods, no added sugar ever, significantly lower your carbohydrate intake and replace with healthy fats and proteins/veggies, don’t drink alcohol or smoke, DO NOT for the love of god eat fast food, get quality sleep, supplement vitamin D and magnesium if needed, drink echinacea and elderberry tea as needed, do your best to unplug and reduce your stress, exercise…. yoga etc…good luck and god speed.

    • Jonathan

      I’m happy you haven’t been infected. Stories like yours inspire people in the wrong way, though, especially with your implication that you can take 0 precautions and not get infected (which I’m sure isn’t your case)

      If 50% of people are fully vaccinated, it cuts suffering by almost 50%. If 85-90% of people are fully vaccinated, the disease has so much trouble jumping ship that the pandemic disappears.

      Of course, it’s impossible to get people on board. A bunch of crybabies that don’t want to wear masks. Covid is always going to be with us, just like the Spanish Flu never really went away. We could get rid of both if we really wanted to.

      • Human

        Jonathan, I did not say that I take no precautions. I don’t have an issue wearing a mask especially in high risk areas. My point is that leadership in society is pushing vaccination as the first line and in some cases only line of defense. This has proven to be dubious and shortsighted. Our population is in very poor physical and mental health and has been since before the sars-cov2 pandemic. Where was the motivation and call to lift people into better physical condition as a first line of defense? Why are we so fixated on a pharmacological intervention for everything? Oh yeah silly me, I forgot that there’s a lot of darn money to be made off of sick people staying sick. In the beginning of 2020 when the crisis began and no one knew just how dangerous this was, I was given inadequate PPE and promptly sent into a Covid triage unit. The fear I experienced was something I hope to never experience again. Do you know what it’s like to rely on uv rays from the sun as your best defense? I made a decision that day. I was going to do everything in my power to learn how to better my chances of not getting seriously ill. I read through study after study of things that demonstrated effective mitigation against Corona type viral infections and applied them. The narrative is that there is nothing you can do and your only hope is to get 1,2,3,4, indefinite vaccinations. This is false and many know it. There are no promises in life, but you can exert your own will to help yourself.

    • NJ

      Very high likelihood that you got infected. Absence of anti-bodies does not mean you did not fight off the infection successfully. Our body has several ways of fighting such infection, first mode of defense is within the respiratory tract (“mucus”). After that, you also have T-cells. So you may not have anti-bodies and still be immune to Covid, but there’s not test for that. And our “medical/scientific” community falsely claims that people like you did not get infected, even though the most we can claim is that “we don’t know whether or not you got infected”. Absence of proof does not mean a something is false.

      • Human

        Hi NJ, yes it really does depend on how you define infection. Spike protein antigen test may come up positive for detecting the protein in your nasal cavity, but does that prove respiratory tract infection? It does not, but many establishments will deem it so. If my innate immune system is highy regulated and manages to continually fight off deeper infections to the point where I exhibit no symptoms and produced no detectable antibodies, then was I “infected”. I suppose it’s possible that prior corona type viral infections have given me a strong T-cell response, but more research is needed on that front.

    • Christopher Crawford

      Kill yourself, dont worry, death doesnt exist, its a lie perpetrated by pricks like you trying to profit off of others

      • Human

        Christopher Crawford, I find your comment confusing. Hope it all works out for you.

  • Cory

    Had covid a little over a year ago. Got vaccinated. Got Covid again last month. These people have no clue what they are talking about.

  • William Moore

    I agree with Michael Q. Rudnin, this article has one dangerous mis-statement which needs to be pointed out.

    “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.”

    If you opt for “infected-and-then-vaccinated”, then your immune system will not be prepared for subsequent Covid-19 infection and so you risk getting a severe case of the disease. This can result in death, short- and long-term disability, or just a lot of discomfort fighting off the disease. If you opt for “vaccinated-and-then-infection”, then in at least 93% of these cases you will be spared a severe infection; protecting you from death and disability. This assumes, of course you get 2 or 3 vaccine shots scheduled as recommended to allow your immune system the time needed to develop antibodies, memory B-cells and memory T-cells against Covid-19.

    By getting the vaccine shots as scheduled before getting Covid-19, most people will avoid severe consequences of getting the disease. That’s a BIG difference!

  • William Moore

    The concept that vaccines prevent infections is just plain wrong. With maybe one or two exceptions vaccines for all diseases have never been able to prevent infection. What vaccines do is to prepare your immune system by educating them as to what to be on the watch for and when the infection is discovered to mount a multi-faceted attack against the infectious agent and infected cells. Thus the concept of a “breakthrough infection” is a misnomer. It is just a infection. Usually each time you get re-infected, the body’s immune system will get smarter and smarter about how to recognize the infectious agent and infected cells and be able to present better targeting antibodies and T-cells. Just because you have been vaccinated does not mean you will not get infected, but what is likely is that your second and third infections will be much milder.

  • Aztek'ah Princess22

    I may be wrong but I think it needs to be this way so where half of the world is unvaccinated and the other vaccinated so that this virus will meet up and cancel each other out🙏🌏🤲😴😴😴🌈🎨🤲🌏🦋🌸