Increased fucose digestion by bacteria in the gut prior to vaccination was associated with reduced numbers of vaccine-activated T-cells, the scientists report.
is an important type of blood immune cell that is activated by a particular strain of bacteria or virus and then replicates to fight infection.
It also highlights the importance of the trillions of bacteria in our guts, collectively called us.
‘— we have immune health and adds a missing piece to the puzzle of why vaccines are so effective from person to person.
Although this study focused on the response to the COVID-19 Pfizer mRNA vaccine, the researchers believe their results may be relevant to other mRNA vaccines in development that protect against other infectious diseases and even cancer.
In this study, researchers collected stool samples and multiple blood samples from 96 healthy participants living in Okinawa, starting before the first dose of the vaccine and ending one month after the second dose.
Why does the immune response to the COVID-19 vaccine change?
They then conducted an extensive analysis, looking at all genes from immune cells in the blood and bacteria in the gut to see if there were any associations with an individual’s T-cell and antibody levels. They found no significant association with antibody levels, but found that individuals with lower T-cell responses had gut microbiomes with higher activity of fucose digestion.
They also found that individuals with reduced T-cell responses had higher expression of two genes, FOS and ATF3, before vaccination. These genes are expressed by blood immune cells and encode proteins that are part of a larger group called AP-1 transcription factors.
Previous studies have shown that different AP-1 transcription factors control T-cell survival and function, but the precise role and function of these two proteins remain unknown.
Individuals with higher FOS and ATF3 expression before vaccination also had microbiomes with higher activity of fucose digestion, suggesting that the effect of the gut on the immune system is through a pathway involving FOS and ATF3.
The mechanism has yet to be proven, but they suggest that fucose digestion leads to increased basal expression of FOS and ATF3 in blood immune cells, which in turn attenuates the response to the COVID-19 vaccine.
The researchers now plan to experimentally manipulate gut bacteria in mice and investigate the exact mechanism of FOS and ATF3 to better understand the relationship between the microbiome, blood immune cells and the overall immune response.