New Cell study uncovers why mRNA vaccines are so effective against COVID-19

The haze of the COVID-19 epidemic still hangs over human society and has yet to subside. As the northern hemisphere enters the cold season and a new mutant strain of Omicron emerges, a new wave of neo-crown epidemics seems to be emerging.

Since the approval of the first vaccine in early 2020, vaccine has significantly curbed the overly rapid spread of the COVID-19 epidemic. Among these, mRNA vaccine has gotten a lot of press. Pfizer/BioNTech and Moderna's mRNA vaccines are arguably the most effective COVID-19 vaccines to date.

Both vaccines were found to be more than 90% effective in preventing symptomatic infections in clinical trials and were approved for marketing by the FDA. Although the development of Delta and Omicron mutant strains has increased the number of breakthrough infections, these two mRNA vaccines are still very effective in reducing hospitalization and mortality in persons with SARS-CoV-2 infections. This has motivated scientists to investigate why mRNA vaccines are so successful, as well as whether the protection they provide can be maintained when new variants emerge.

On December 23, 2021, researchers at the University of Washington School of Medicine and St. Jude Children's Research Hospital published a study in Cell titled: SARS-CoV-2 mRNA vaccination elicits a robust and persistent T follicular helper cell response in humans.

The follicular helper T cell (TFH), which supports antibody-forming cells in creating huge numbers of progressively stronger antibodies while also boosting immunological memory, is significantly and continuously activated by mRNA vaccines, according to this study. Antibody-producing long-lived cells and memory B cells help provide protection against severe disease and death once TFH cells have declined. Furthermore, many follicular helper T cells are activated by a fraction of the virus, a viral component that is not found mutated even in the highly mutated Omicron variant.

The research explains why mRNA vaccinations create such high amounts of neutralizing antibodies and implies that vaccination can help many people produce effective antibodies even when the virus evolves.

"The longer the follicular helper T cells provide help, the more likely you are to have a good memory response," said Philip Mudd, Ph.D., corresponding author of this study. "In this study, it was found that the response of these follicular helper T cells persisted. What's more, some of them would respond to a part of the viral spike protein that had very little variation."

The researchers enlisted 15 volunteers to get two doses of Pfizer's mRNA vaccine, three weeks apart, in this latest study. The germinal centers of the volunteers' lymph nodes were taken 21 days after the first dose, soon before the second, and then on days 28, 35, 60, 110, and 200. At the outset of the trial, none of the participants had been infected with SARS-CoV-2.

The T-cell receptor sequence and the phenotypic of follicular helper cells were studied and evaluated. Researchers discovered that individuals with this allele elicited a large immunological response to the 167-180 motif of SARS-CoV-2 S protein, one of the most common HLA alleles in humans, via mining T-cell receptor retention in responding follicular helper T cells.

Furthermore, while circulating S protein-specific follicular helper T cells peaked one week after the second immunization, S protein-specific TFH cells remained at an almost constant frequency for at least 6 months, according to paired blood and lymph node data. This finding underscores the importance of follicular helper T cell responses in mRNA vaccine long-term immunization.

The researchers say they'll investigate what happens following a booster dose of the COVID-19 mRNA vaccine, as well as whether alterations in follicular helper T cells could explain why patients with weakened immune systems, such as those with AIDS, don't produce robust antibody responses.

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