Why are mRNA vax effective against severe Covid?

The vaccines have arguably been the most effective Covid vaccines developed to date. In clinical trials, both were more than 90 per cent effective in preventing symptomatic infection.

Even with the Delta and Omicron variants, the vaccines remain quite effective at preventing hospitalisation and deaths.

In the study, researchers from Washington University School of Medicine in St. Louis and St. Jude Children's Research Hospital showed that the Pfizer vaccine strongly and persistently activates a kind of helper immune cell that assists antibody-producing cells in creating large amounts of increasingly powerful antibodies, and also drives the development of some kind of immune memory.

Known as T follicular helper cells, these cells last for up to six months after vaccination, helping the body crank out better and better antibodies. Once the helper cells decline, long-lived antibody-producing cells and memory B cells help to provide protection against severe disease and death, the researchers said.

Further, many of the T follicular helper cells are activated by a part of the virus that doesn't seem to pick up mutations, even in the highly mutated Omicron variant.

The findings, published in the journal Cell, help explain why the Pfizer vaccine elicits such high levels of neutralising antibodies and suggests that vaccination may help many people continue producing potent antibodies even as the virus changes.

"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," said Philip Mudd, Assistant Professor of emergency medicine at Washington University.

"In this study, we found that these T follicular helper cell responses just 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," Mudd said.

In the study, the team aimed to understand the role of T follicular helper cells in producing such a strong germinal centre response.

The researchers recruited 15 volunteers who each received two doses of the Pfizer vaccine three weeks apart. The volunteers underwent a procedure to extract germinal centres from their lymph nodes 21 days after the first dose, just before the second dose; then at days 28, 35, 60, 110 and 200 after the initial dose.

None of the volunteers had been infected with SARS-CoV-2 at the start of the study. The researchers obtained T follicular helper cells from the lymph nodes and analysed them.

The researchers are now studying what happens after a booster dose and 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.