Researchers have found evidence that the immune response to vaccines like the first two for COVID-19 is both strong and potentially long-lasting.
The vaccines used a technology that had never before been used in Food and Drug Administration-approved vaccines. Both vaccines performed well in clinical trials, and both have been widely credited with reducing disease, but concerns remain over how long immunity induced by the new vaccine technology will last.
In the new study, researchers found that nearly four months after the first dose, people who received the Pfizer vaccine still had so-called germinal centers in their lymph nodes churning out immune cells directed against SARS-CoV-2, the virus that causes COVID-19. Germinal centers, which form as the result of natural infection or vaccination, are boot camps for immune cells, a place where inexperienced cells are trained to better recognize the enemy and weapons are sharpened. A better germinal center response may equal a better vaccine.
Moreover, vaccination led to high levels of neutralizing antibodies effective against three variants of the virus, including the Beta variant from South Africa that has shown some resistance to vaccines. Vaccination induced stronger antibody responses in people who had recovered from SARS-CoV-2 infection compared to those who had never been infected.
‘Truly remarkable’ findings
In April, both Pfizer and Moderna reported that their vaccines provided at least six months of protection. Their reports were based on tracking whether vaccinated people came down with COVID-19. Other groups have monitored antibody levels in the blood and concluded that the vaccine provides at least months of protection. But nobody had looked to see how the immune response was developing in the body, which could provide important clues to the strength and persistence of the immune response without requiring years of follow-up.
“Germinal centers are the key to a persistent, protective immune response,” says senior author Ali Ellebedy, associate professor of pathology and immunology, of medicine and of molecular microbiology at Washington University in St. Louis.
“Germinal centers are where our immune memories are formed. And the longer we have a germinal center, the stronger and more durable our immunity will be because there’s a fierce selection process happening there, and only the best immune cells survive. We found that germinal centers were still going strong 15 weeks after the vaccine’s first dose. We’re still monitoring the germinal centers, and they’re not declining; in some people, they’re still ongoing. This is truly remarkable.”
Scientists don’t fully understand why some vaccines, such as the one for smallpox, induce strong protection that lasts a lifetime, while others, such as the vaccine for whooping cough, require regular boosters. But many suspect that the difference lies in the quality of the germinal centers induced by different vaccines.
COVID-9 vaccine response
Scientists created the Pfizer and Moderna vaccines with mRNA technology. Unlike most vaccines, which provide bits of viral or bacterial proteins to trigger an immune response, mRNA-based vaccines provide instructions for the body to build and release foreign proteins, such as the spike protein in the case of the SARS-CoV-2 virus.
To assess whether this new kind of vaccine induces a good germinal center response, Ellebedy and co-first author Jackson Turner, an instructor in pathology and immunology, teamed up with co-senior author Rachel Presti, associate professor of medicine, and co-first author Jane O’Halloran, assistant professor of medicine, and started the study once the first COVID-19 vaccine became available in mid-December 2020.
The team enlisted the help of coauthors Sharlene Teefey, and William Middleton, both professors of radiology, to perform ultrasound-guided sampling of the minuscule germinal centers in lymph nodes in the armpit. Teefey and Middleton extracted cells from 14 people who received the Pfizer vaccine. They obtained samples three weeks after the first dose (just prior to administration of the second dose), and at weeks four, five, and seven. Ten of the participants gave additional samples 15 weeks after the first dose. None of the participants previously had 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 producing antibodies that target a key SARS-CoV-2 protein. The response expanded greatly after the booster shot and then stayed high. Even 15 weeks after the first dose, eight of 10 people still had detectable germinal centers containing B cells targeting the virus.
“This is evidence of a really robust immune response,” Presti says. “Your immune system uses germinal centers to perfect the antibodies so they can bind well and last as long as possible. The antibodies in the blood are the end result of the process, but the germinal center is where it is happening.”
The researchers also obtained blood samples from 41 people who received the Pfizer vaccine, including eight who previously had been infected with the virus that causes COVID-19. They obtained samples prior to the administration of each dose of the vaccine, 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 one week after the second. People who previously had been infected already had antibodies in their blood before the first dose. Their levels shot up quickly after the first dose and peaked higher than the uninfected participants’ levels.
“We didn’t set out 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,” O’Halloran says. “If you’ve already been infected and then you get vaccinated, you get a boost to your antibody levels. The vaccine clearly adds benefit, even in the context of prior infection, which is why we recommend that people who have had COVID-19 get the vaccine.”
The study appears in the journal Nature.
The National Institute of Allergy and Infectious Diseases of the National Institutes of Health, 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 Helen Hay Whitney Foundation postdoctoral fellowship funded the work. This study used samples obtained from the Washington University School of Medicine’s COVID-19 biorepository supported by the NIH/National Center for Advancing Translational Sciences.
