Scientists Explore How Immune Memory Cells Function Post-Vaccination

Vaccines provide our immune systems with protection and memory of infection, allowing our bodies to kill off pathogens before they cause severe symptoms. While much has been discovered about the antibodies made in our blood post-vaccination, how and when they are generated has remained unclear. That’s why a team of researchers from Monash University’s Immune Memory Laboratory investigated where these immune memory cells travel several weeks after immunization.

While the body’s lymph nodes, tonsils, and gut have all been identified as locations where these “long-lived plasma cells” are produced, the mechanism by which some vaccines cause these cells to persist for decades has remained a mystery. After the widespread research and dispersal of COVID-19 vaccines, uncovering these cellular processes has an increased global need.

The team, spearheaded by Dr. Marcus Robinson and Professor David Tarlinton, recently published their findings in the journal Science Immunology. The group began by using mouse models expressing a fluorescent protein, called the TdTomato protein, only in cells producing antibodies against a specific vaccine.

Using a genetic system called “timestamping,” the researchers could see how memory cells are stored in the bone marrow of mice in real-time. This technique allowed them to mark all the fluoresced plasma cells present after vaccination, then return later to see which cells survived. By regularly repeating this process post-vaccination, the team could generate a detailed recounting of where the cells traveled and how long they lived.

According to Professor Tarlinton, studying these individual cells as they are born, mature, and stored to protect against repeat invasion by a specific pathogen “…can inform our understanding of how the recruitment of long-lived plasma cells occurs.”

Mapping these cells revealed that one vaccination in mice generated 40,000 persisting plasma cells in the bone marrow. After the initial flourish, these cells declined at a rate of 0.1% daily, with a half-life of approximately 700 days. This provided an estimate of the duration of protection, plus identified avenues of future study for these long-lived cells.

Professor Tarlinton believes that understanding how these long-lived plasma cells are generated, live and die “…will inform our ability to modulate their recruitment, through different vaccine combinations or delivery strategies – ultimately allowing us to be able to increase the longevity of immunity.”

“In fact, there is exciting work recently reported in Nature that describes how altering the mechanics of vaccination can dramatically influence the character of the immune response, and we would predict the production of these special cells that have been the focus of our work,” Professor Tarlinton says.