October 4, 2023

The vaccines from Pfizer-BioNTech and Moderna trigger a sustained immune response in the body that can protect against the coronavirus for years, scientists reported on Monday.

The results add to the growing evidence that most people immunized with the mRNA vaccines may not need a booster dose as long as the virus and its variants do not progress much beyond their current forms – which is not guaranteed. People who have recovered from Covid-19 before they were vaccinated may not need a booster vaccination, even if the virus goes through a significant transformation.

“It’s a good sign of how persistent our immunity to this vaccine is,” said Ali Ellebedy, an immunologist at Washington University in St. Louis who led the study, which was published in the journal Nature.

The study did not take into account the coronavirus vaccine manufactured by Johnson & Johnson, but Dr. Ellebedy said he expected the immune response to be less permanent than that of mRNA vaccines.

Dr. Ellebedy and colleagues reported last month that in people who survived Covid-19, immune cells that recognize the virus remain dormant in the bone marrow for at least eight months after infection. A study by another team showed that so-called memory B cells continue to mature and strengthen for at least a year after infection.

Based on these results, the researchers suggested that immunity in people infected with the coronavirus and later vaccinated could last for years, possibly a lifetime. However, it was unclear whether vaccination alone could have a similar long-lasting effect.

Dr. Ellebedy explored this question by examining the source of memory cells: the lymph nodes, where immune cells train to recognize and fight the virus.

After an infection or vaccination, a specialized structure forms in the lymph nodes, the germinal center. This structure is a kind of elite school for B cells – a boot camp in which they become increasingly sophisticated and learn to recognize a multitude of viral genetic sequences.

The greater the range and the longer these cells have to practice, the more likely they are to thwart any virus variants that may appear.

“Everyone is always focused on developing the virus – this shows that the B cells are doing the same thing,” said Marion Pepper, an immunologist at the University of Washington in Seattle. “And it will protect against the continued development of the virus, which is really encouraging.”

After an infection with the coronavirus, the germinal center forms in the lungs. But after the vaccination, the cells are formed in the lymph nodes in the armpits that researchers can reach.


June 28, 2021, 5:59 p.m. ET

Dr. Ellebedy and colleagues recruited 41 people – including eight with a history of infection with the virus – who were immunized with two doses of the Pfizer BioNTech vaccine. The team collected lymph node samples from 14 of these people three, four, five, seven and 15 weeks after the first dose.

This meticulous work makes this a “heroic study,” said Akiko Iwasaki, an immunologist at Yale. “This kind of careful time history analysis in humans is very difficult.”

Dr. Ellebedy found that 15 weeks after the first dose of the vaccine, the germinal center was still highly active in all 14 participants and the number of memory cells that recognized the coronavirus had not decreased.

“The fact that the reactions lasted almost four months after the vaccination – that’s a very, very good sign,” said Dr. Ellebedy. Sprouting centers typically peak one to two weeks after vaccination and then decrease.

“Usually there isn’t much left after four to six weeks,” said Deepta Bhattacharya, an immunologist at the University of Arizona. But germinal centers stimulated by the mRNA vaccines “still go in, months, and most people don’t go back much”.

Dr. Bhattacharya noted that most of what scientists know about the persistence of germinal centers is based on animal studies. The new study shows for the first time what happens to people after vaccination.

The results suggest that the vast majority of those vaccinated will be protected in the long term – at least against the existing coronavirus variants. But older adults, people with weak immune systems, and those taking drugs that suppress immunity may need boosters; People who survived Covid-19 and were later vaccinated may not need it at all.

It is difficult to predict exactly how long protection against mRNA vaccines will last. In the absence of variants that bypass immunity, immunity could theoretically last a lifetime, experts said. But the virus is clearly evolving.

“Anything that would actually require a refresher would be variant-based, not immunity waning,” said Dr. Bhattacharya. “I just don’t see it.”

People who have been infected with the coronavirus and then immunized see a sharp spike in their antibody levels, likely because their memory B cells – which produce antibodies – had many months to develop before vaccination.

The good news: a booster vaccine is likely to have the same effect on people who have been vaccinated as a previous infection, said Dr. Ellebedy. “If you give them another chance to get involved, they’ll have a massive response,” he said, referring to memory B cells.

In terms of boosting the immune system, vaccination is “probably better” than recovering from the actual infection, he said. Other studies have shown that the repertoire of memory B cells produced after vaccination is more diverse than that produced by infection, suggesting that the vaccines protect against variants better than natural immunity alone.

Dr. Ellebedy said the results also suggested that these signs of sustained immune response could be caused by mRNA vaccines alone, as opposed to those made in more traditional ways like Johnson & Johnson’s.

But that’s an unfair comparison because the Johnson & Johnson vaccine is given as a single dose, said Dr. Iwasaki: “If the J&J had a booster, they might get the same kind of reaction.”