Green and blue coronavirus cells under magnification intertwined with DNA cell structure
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People who received mRNA vaccines against SARS-CoV-2 after a COVID-19 infection produced a large number of protective CD8 T cells, researchers at the University of Washington School of Medicine in Seattle have found.

Their work was published last week in Nature Immunology.

The finding may explain why people who have acquired immunity against the virus from both natural infection and vaccination—so-called hybrid immunity—are better able to resist reinfection than are those who have acquired their immunity from either infection or vaccination alone, said David Koelle, a professor of medicine, Division of Allergy and Infectious Diseases, at the UW School of Medicine, who led the research team.

“We found that receiving the standard initial mRNA vaccine two-dose series after having been infected not only boosts memory immune cells acquired during the original infection, but also elicits the production of a diverse population of new cells as well,” said Koelle. This diversity could help protect against new variants of the virus that may emerge after the first infection, he added.

There has been a lot of debate about whether vaccines, prior infection, or both confer the best protection against COVID 19.

In this study, the researchers followed 53 people who had become infected with SARS-CoV-2 early in the pandemic before vaccines became available. The scientists collected blood samples as the patients recovered from their infections and then after they received the first two mRNA vaccines and then a follow-up booster. 

This team focused on T cells, and, in particular, CD8 T cells. These play an essential role by directly limiting viral replication and bind to portions of foreign proteins. When this happens, the cells begin to proliferate, generating an army of clones that target and destroy infected cells. In the case of SARS-CoV-2 mRNA vaccines, T cells bind to portions of the spike protein that the virus uses to latch onto and invade cells.

The sequences of the T cell receptors vary so it is possible to identify different clone populations by sequencing their receptor genes. Koelle and his colleagues were able to do this with the help of the Seattle-based biotech company Adaptive Biotechnologies, which donated its sequencing services for the project.

Using these sequences as a kind of barcode for each CD8 T cell clone, the researchers were able to determine that, as expected, the number of CD8 T cells that had been generated in response to the initial infection fell as immunity waned.

With vaccination, however, the number of CD8 T cells targeting spike protein jumped. This was in part due to the activation of clones descended from the CD8 T cells generated by the initial infection.

“This indicates that receiving an mRNA vaccine after infection not only boosts the numbers of the memory immune cells acquired during the original infection, but also elicits the production of a diverse population of new clones as well,” Koelle said.

The fact that CD8 cells numbers and diversity jumped after the mRNA vaccination is important for vaccine development because CD8 cells do not respond to many currently available types of vaccines, according to Koelle.

“Researchers in the vaccine field have been looking for ways to elicit potent CD8 T cell response for many years,” he said. “Currently, only live virus vaccines, such as measles, mumps and rubella and the oral polio vaccines, have been able to do that. But they, being live, raise safety concerns and are expensive to make. Now, we have documented that these mRNA vaccines, which are relatively cheap and are flexible, are good CD8 boosters.”

Koelle told Inside Precision Medicine, “If you have had COVID-19, you should get vaccinated anyway.  The CD8 T cell response is largely cross-reactive and therefore cross-protective against variant strains of SARS-CoV-2, while in contrast, the antibody responses that one gets after COVID-19 infection is largely strain-specific and does not provide very good protection against re-infection.”

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