COVID-19 vaccine generates immune structures essential for long-lasting immunity – Washington University School of Medicine in St. Louis


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Vaccines likely induce strong and persistent immunity to COVID-19

Matt Miller

The first two COVID-19 vaccines cleared for emergency use by the Food and Drug Administration (FDA) used technology that had never been used before in vaccines approved by the FDA. Both vaccines have performed well in clinical trials, and both have been widely recognized as having reduced disease, but concerns remain about the duration of immunity induced by new vaccine technology.

Now, a study by researchers at Washington University School of Medicine in St. Louis, published June 28 in the journal Nature, has found evidence that the immune response to such vaccines is both strong and potentially long lasting. Almost four months after the first dose, people who received the Pfizer vaccine still had so-called germ centers in their lymph nodes producing immune cells directed against SARS-CoV-2, the virus that causes COVID-19. . Germ centers, which form as a result of natural infection or vaccination, are training camps for immune cells, a place where inexperienced cells are trained to better recognize the enemy and weapons are sharpened. A better response from the germinal center can equal a better vaccine.

In addition, the vaccination led to high levels of neutralizing antibodies effective against three variants of the virus, including the beta variant from South Africa which has shown some resistance to the vaccines. Vaccination elicited stronger antibody responses in people who had recovered from SARS-CoV-2 infection compared to those who had never been infected.

In April, Pfizer and Moderna reported that their vaccines offered protection for at least six months. Their reports were based on tracking whether those vaccinated had contracted COVID-19. Other groups have monitored antibody levels in the blood and concluded that the vaccine offers at least months of protection. But no one had watched how the immune response developed in the body, which could provide important clues about the strength and persistence of the immune response without requiring years of monitoring.

“Germ centers are the key to a protective and persistent immune response,” said senior author Ali Ellebedy, PhD, associate professor of pathology and immunology, medicine and molecular microbiology. “The germinal centers are where our immune memories are formed. And the more germinal center we have, the stronger and longer our immunity will be because there is a fierce selection process going on there, and only the best immune cells survive. We found that the germinal centers were still strong 15 weeks after the first dose of the vaccine. We are still watching the germinal centers, and they are not diminishing; in some people, they are still ongoing. It is truly remarkable. “

Scientists don’t fully understand why some vaccines, like the smallpox vaccine, induce strong, lifelong protection, while others, like the pertussis vaccine, require regular boosters. But many suspect that the difference lies in the quality of the germinal centers induced by the different vaccines.

The Pfizer and Moderna vaccines were created with mRNA technology. Unlike most vaccines, which provide pieces of viral or bacterial protein to trigger an immune response, mRNA-based vaccines provide instructions to the body to build and release foreign proteins, such as the spike protein in the body. case of the SARS-CoV-2 virus. To assess whether this new type of vaccine induces a good germinal center response, Ellebedy and co-first author Jackson Turner, PhD, instructor in pathology and immunology, teamed up with co-lead author Rachel Presti, MD, PhD, associate professor of medicine, and co-first author Jane O’Halloran, MD, PhD, assistant professor of medicine, and began the study once the first COVID-19 vaccine became available in mid-December 2020.

The team enlisted the help of co-authors Sharlene Teefey, MD, and William Middleton, MD, both professors of radiology, to perform ultrasound-guided sampling of tiny germ centers in lymph nodes in the armpit. Teefey and Middleton extracted cells from 14 people who received the Pfizer vaccine. Samples were obtained three weeks after the first dose (just before the second dose was given) and at weeks four, five and seven. Ten of the participants gave additional samples 15 weeks after the first dose. None of the participants had previously been infected with the virus that causes COVID-19.

Three weeks after the first dose, all 14 participants had formed germinal centers with B cells that produce antibodies that target a key SARS-CoV-2 protein. The response widened considerably after the recall and then remained high. Even 15 weeks after the first dose, eight in ten people still had detectable germinal centers containing B cells targeting the virus.

“It’s evidence of a really robust immune response,” Presti said. “Your immune system uses germinal centers to perfect the antibodies so that they can bind well and last as long as possible. Antibodies in the blood are the end result of the process, but the germinal center is where it happens.

The researchers also obtained blood samples from 41 people who received the Pfizer vaccine, including eight who had previously been infected with the virus that causes COVID-19. Samples were taken before each dose of the vaccine was administered, as well as at weeks four, five, seven and 15 after the first dose. In people without prior exposure to the virus, antibody levels rose slowly after the first dose and peaked a week after the second. People who had already been infected already had antibodies in their blood before the first dose. Their levels rose rapidly after the first dose and peaked higher than the levels of uninfected participants.

“We did not attempt to compare the effectiveness of vaccination in people with and without a history of infection, but when we looked at the data, we could see an effect,” said O’Halloran. “If you’ve been infected in the past and get vaccinated, your antibody level will go up. The vaccine clearly adds a benefit, even against the background of a previous infection, which is why we recommend that people who have had COVID-19 get vaccinated. “

Turner JS, O’Halloran JA, Kalaidina E, Kim W, Schmitz AJ, Zhou JQ, Lei T, Thapa M, Chen RE, Case JB, Amanat F, Rauseo AM, Haile A, Xie X, Klebert MK, Suessen T, Middleton WD, Shi PY, Krammer F, Teefey SA, Diamond MS, Presti RM, Ellebedy AH. SARS-CoV-2 mRNA vaccines induce persistent germinal center responses in humans. Nature. June 28, 2021. DOI:

This study was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH), grant and contract numbers U01AI141990, 1U01AI150747, R01 AI157155, AI134907, 5T32CA009547, HHSN272201400006C, HHSN19C27220193000006C, HHSN19C27220193000006C, HHSN19C27220193000006C, HHSN19C27220193000006C, HHSN19C272201400006C; the NIH, license number UL1TR001439; the Sealy & Smith Foundation; the Kleberg Foundation; the John S. Dunn Foundation; the Amon G. Carter Foundation; the Gilson Longenbaugh Foundation; the Summerfield Robert Foundation; and a postdoctoral fellowship from the Helen Hay Whitney Foundation. This study used samples obtained from the Washington University School of Medicine COVID-19 biodepot, supported by NIH / National Center for Advancing Translational Sciences, grant number UL1 TR002345.

The 1,500 physicians at the Washington University School of Medicine are also on the medical staff at Barnes-Jewish and St. Louis Children’s Hospitals. The School of Medicine is a leader in medical research, education, and patient care, consistently ranking among the nation’s top medical schools by US News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s Hospitals, the School of Medicine is linked with BJC HealthCare.

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