Study explains what makes mRNA vaccines so effective against COVID-19

Shots trigger exceptional antibody response by activating key helper immune cells.

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Pfizer/BioNTech and Moderna COVID-19 vaccines are the first two vaccines created with mRNA vaccine technology. Both vaccines are found to be the most effective COVID-19 vaccines. Both vaccines are found more than 90% effective at preventing symptomatic infection.

The success of the new technology has led scientists to figure out why mRNA vaccines are so effective and whether the protection they provide is likely to endure as new variants arise.

Scientists at Washington University School of Medicine in St. Louis and St. Jude Children’s Research Hospital shed light on the quality of the immune response triggered by mRNA vaccines. They show that the Pfizer vaccine strongly and persistently actuates a kind of helper immune cell that aids antibody-producing cells in creating large amounts of increasingly powerful antibodies. The vaccine also drives the development of some types of immune memory.

These helper cells are T follicular helper cells, which last for up to six months after vaccination, helping the body crank out better and better antibodies. Once the helper cells are reduced, the long-lived antibody-producing cells and memory B cells protect against severe disease and death.

Co-corresponding author Philip Mudd, MD, Ph.D., an assistant professor of emergency medicine at Washington University, said“The longer the T follicular helper cells provide help, the better the antibodies are and the more likely you are to have a good memory response. In this study, we found that these T follicular helper cell responses keep going and going.”

“And what’s more, some of them are responding to one part of the virus’s spike protein that has very little variation in it. With the variants, especially delta and now omicron, we’ve been seeing some breakthrough infections, but the vaccines have held up very nicely in terms of preventing severe disease and death. I think this strong T follicular helper response is part of the reason why the mRNA vaccines continue to be so protective.”

The main antibodies created in light of infection or vaccination are not good. B cells need to undergo so-called germinal centers in the lymph nodes before producing strong antibodies.

T follicular helper cells are the drill sergeants of these germinal centers. The helper cells instruct the antibody-producing cells to make ever more potent antibodies and encourage those with the best antibodies to multiply and, in some cases, turn into long-lived antibody-producing cells or memory B cells. Scientists reported scientists that the longer the germinal centers last, the better and stronger the antibody response.

The study involved 15 volunteers who received doses of the Pfizer vaccine three weeks apart. Scientists then extracted their germinal centers from their lymph nodes 21 days after the first dose, just before the second dose, and then at days 28, 35, 60, 110, and 200 after the initial dose.

Scientists are now studying what happens after a booster dose. They will determine whether changes to T follicular helper cells could explain why people with compromised immune systems, such as those with HIV infection, do not mount a strong antibody response.

Journal Reference:

  1. Philip A. Mudd, Anastasia A. Minervini et al. SARS-CoV-2 mRNA vaccination elicits a robust and persistent T follicular helper cell response in humans. Cell, 2021; DOI: 10.1016/j.cell.2021.12.026