Latest research reveals why mRNA vaccines are so effective for COVID-19

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Latest research reveals why mRNA vaccines are so effective for COVID-19

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Cell: Latest research reveals why mRNA vaccines are so effective for COVID-19.

Since the first COVID-19 vaccine was approved in early 2020, vaccination has greatly suppressed the rapid spread of the COVID-19 epidemic.

Among them, the COVID-19 mRNA vaccine has attracted much attention. The mRNA vaccines developed by Pfizer/BioNTech and Moderna can be said to be the two most effective COVID-19 vaccines so far.

In clinical trials, these two vaccines have an effect of more than 90% in preventing symptomatic infections, and have been approved by the US FDA for marketing.

Although breakthrough infections have increased with the emergence of Delta and Omicron mutant strains, these two COVID-19 mRNA vaccines are still quite effective in preventing hospitalization and death of people living with COVID-19 infections.

This phenomenon has also prompted scientists to try to figure out why mRNA vaccines are so effective and whether the protection they provide can be sustained with the emergence of new variants.

December 23, 2021, Researchers from School of Medicine of the University of Washington and St. Jude Children’s Research Hospital  published a research paper,  entitled: SARS-CoV-2 mRNA vaccination elicits a robust and persistent T follicular helper cell response in humans .

The research shows that mRNA vaccines strongly and persistently activate a kind of helper immune cells- follicular helper T cells (TFH) , which assist antibody-producing cells to produce a large number of more and more powerful antibodies while also promoting some immune memory.

Once TFH cells decline, the long-lived antibody-producing cells and memory B cells will help provide protection against serious diseases and death.

In addition, many follicular helper T cells are activated by a part of the virus, and this virus component is not found to be mutated even in the highly mutated Omicron variant.

This research helps explain why mRNA vaccines can produce such high levels of neutralizing antibodies, and shows that even if the virus changes, vaccination can help many people continue to produce strong antibodies.

Dr. Philip Mudd , the corresponding author of this study , said: “The longer the follicular helper T cells provide help, the better the antibody, and the more likely you are to have a good memory response.

In this study, it was found that these follicles The response of helper T cells has continued. More importantly, some of them will respond to a certain part of the viral spike protein, and this part has very little mutation. “

Research Mode Diagram

In fact, with the emergence of new coronavirus variants, especially Delta and Omicron, we have seen some breakthrough infections, but these vaccines have performed very well in preventing serious illness and death.

Therefore, the research team believes that this powerful immune response of follicular helper T cells is part of the reason why the mRNA vaccine continues to have a protective effect .

The body’s first antibodies produced after infection or vaccination are often not very good. B cells need to be trained by the lymph node germinal center to produce truly powerful antibodies.

The follicular helper T cells are the instructors of these boot camps. Follicular helper T cells provide guidance for B cells to produce stronger antibodies, and encourage those B cells that can produce the best antibodies to continue to proliferate and then remember B cells.

B cells need to go through a training camp germinal center to produce truly powerful antibodies in the lymph nodes, and follicular helper cells are the instructors of these training camps.

Helper cells provide guidance for B cells to produce more powerful antibodies, and encourage those cells with the best antibodies to proliferate and form memory B cells.

Therefore, in general, the longer the germinal center lasts, the better and stronger the antibody response.

Specific flow chart

Earlier this year, Dr. Ali Ellebedy , associate professor of pathology and immunology, medicine and molecular microbiology at the University of Washington , reported that nearly 4 months after people received the first dose of Pfizer mRNA vaccine, they still have germinal centers in their lymph nodes. The germinal center is mass-producing immune cells against SARS-CoV-2.

Now, in this Cell paper, the research team aims to understand the role of follicular helper T cells (TFH) in generating such a strong germinal center response.

After being vaccinated with the mRNA vaccine, the subject has a significant immune response to the motif at positions 167-180 of the S protein of the new coronavirus

In this latest study, the research team recruited 15 volunteers, each receiving two doses of Pfizer’s mRNA vaccine, three weeks apart.

Volunteers extract the germinal centers from their lymph nodes 21 days after the first dose, that is, before the second dose, followed by the 28th, 35th, 60th, 110th and 200th day sky.

At the beginning of the study, none of these volunteers had been infected with SARS-CoV-2.

Timeline of the germinal center for extracting mRNA vaccination volunteers

The researchers analyzed and evaluated the T cell receptor sequence and the phenotype of follicular helper cells.

They found that the excavation of T cell receptor retention of responding follicular helper T cells showed that individuals with this allele had a significant immune response to the motif at positions 167-180 of the new coronavirus S protein.

Alleles are one of the most common HLA alleles in humans.

In addition, paired blood and lymph node specimens showed that although circulating S protein-specific vesicle helper T cells reached a peak one week after the second immunization, S protein-specific TFH cells remained almost maintained for at least 6 months Constant frequency.

This result emphasizes that the follicular helper T cell response plays a key role in the long-term immunity of mRNA vaccines.

S protein-specific THF cells maintain an almost constant frequency for at least 6 months

The research team said that the next plan is to study what happens when the dose of the COVID-19 mRNA vaccine is increased, and whether changes in follicular helper T cells can explain why people with compromised immune systems (such as AIDS patients) do not develop a strong antibody response.

References:

https://doi.org/10.1016/j.cell.2021.12.026

Latest research reveals why mRNA vaccines are so effective for COVID-19

(source:internet, reference only)

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