Saint Louis, MO

COVID-19 vaccine produces immunological components necessary for sustained protection

Steve Chao

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ST. LOUIS, MO — The first two COVID-19 vaccines certified by FDA for emergency use featured a technology never before used in FDA-approved vaccines.

Both vaccines worked well in clinical trials, and both were largely credited with lowering disease, but doubts linger over how long the new vaccine technology will survive.

A study by researchers at the Washington University School of Medicine in St. Louis, published in the journal Nature on June 28, has revealed indications that the immune response to such vaccines is both powerful and potentially long-lasting.

Nearly four months after the first dosage, those receiving the Pfizer vaccination still had so-called germinal centers in their lymph nodes churning out immune cells aimed against SARS-CoV-2, the virus responsible for COVID-19.

Both Pfizer and Moderna claimed their April immunizations provided at least six-month protection. Their reports were based on the following COVID-19-vaccinated people.

Other groups tracked blood antibody levels, concluding the immunization provides at least months of protection. But no one looked at how the immune response grew in the body, which could provide significant indications of the strength and persistence of immune response without requiring years of follow-up.

“Germinal centers are the key to a persistent, protective immune response,” said senior author Ali Ellebedy, Ph.D., associate professor of pathology and immunology, medicine and molecular microbiology. “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 entirely understand why some vaccines, such as the smallpox vaccine, elicit life-long protection, while others, such as the whooping cough vaccine, require regular doses. But many assume the difference is the quality of germ centers created by different vaccines.

Pfizer and Moderna vaccines were developed using mRNA technology. Unlike conventional vaccinations that offer pieces of viral or bacterial proteins to induce an immune response, mRNA-based vaccines provide instructions for the body to produce and release foreign proteins, such as SARS-CoV-2 spike protein.

Co-authors Sharlene Teefey, MD, and William Middleton, MD, both radiology professors, helped the researchers to do an ultrasound-guided sampling of the tiny germ foci in the armpit lymph nodes.

Teefey and Middleton collected cells from 14 receiving the Pfizer vaccine. Samples were taken immediately before the second dose and four, five and seven weeks afterward. Ten subjects supplied samples 15 weeks following the first dose. No individuals had previously been infected with the COVID-19 virus.

Three weeks after the initial treatment, all 14 participants established germ centers with B-cells generating antibodies targeting a crucial SARS-CoV-2 protein.

“This is evidence of a really robust immune response,” Presti said. “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.”

Researchers also collected blood samples from 41 people getting the Pfizer vaccine, including eight already infected with COVID-19. Samples were obtained before each dose and four, five, seven and 15 weeks after the first dose.

In individuals without previous virus infection, following the first dose, antibody levels grew moderately and peaked one week after the second. Before the initial therapy, people affected had antibodies in their blood. Their levels surged shortly after the first treatment, rising above uninfected patients.

“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 said. “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.”

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