Vaccine efficacy could be enhanced using new insights about the immune system, researchers say.
Immunologists at St. Jude Children’s Research Hospital have discovered a biological pathway that selectively controls how key immune cells, known as T follicular helper cells, mature into functional components of the immune system. This finding, researchers hope, could lead to the development of drugs to activate the metabolic pathway to enhance the effectiveness of vaccines, including those that protect against COVID-19.
The research has been published in the journal Nature.
A key pathway
The study, led by Hongbo Chi, Ph.D. of the Department of Immunology, sought to discover whether a metabolic control pathway existed that modified the T follicular helper cells to activate them. When such cells are activated, they help antibody-producing cells, called B cells, to mature and to generate infection-fighting antibodies.
To determine a possible control pathway, Chi and his colleagues used genetic techniques to delete in the T cells multiple enzymes known to be elements of such metabolic control pathways. The scientists then introduced the deletion-engineered T cells into mice followed by infection with a virus and tested whether the T cells lacking the enzyme were functional.
Their experiments revealed that one metabolic control pathway, called the CDP-ethanolamine pathway, selectively regulated the T follicular helper cells.
“This finding was a big surprise,” Chi said.
“First of all, this pathway was considered to have a housekeeping function leading to the production of building blocks for the cell membrane. But we discovered that it has a major signalling function. And secondly, we were surprised that this pathway – and not other parallel pathways of this type –was the only one involved in regulating T follicular helper cells.”
As an additional method to determine if the pathway selectively regulated the T follicular helper cells, the researchers deleted each of the key enzymes they identified in the CDP-ethanolamine pathway. They found that deletion of these enzymes, but not those of other parallel regulatory pathways, selectively impaired development of the T follicular helper cells, but not overall immune function.
Drugs to modify the immune system and its vaccine response
Chi noted that, importantly, those key enzymes could be targets for drugs that either enhance or inhibit the pathway, and therefore impact the activity of the T cells.
“We are now exploring whether we can enhance the effectiveness of vaccines by using drugs that activate the pathway, to help these T cells mobilise the immune system to generate antibodies in response to a vaccine.
“On the other hand, to treat autoimmune disease, we’re interested in developing new ways to inhibit this pathway,” he said. “This approach is promising because we know that such activation or inhibition is highly selective for T follicular helper cells and would not affect other immune functions, Chi continued.
