byPerelman School of Medicine at the University of Pennsylvania

Credit:Cell(2025). DOI: 10.1016/j.cell.2025.11.023

mRNA vaccines, such as those used against COVID-19, are effective at generating antibody responses. These antibodies are produced through specialized immune structures called germinal centers, but until now it was not fully understood how mRNA vaccines trigger this powerful process.

In a studypublishedinCell, researchers from the Perelman School of Medicine at the University of Pennsylvania reveal that both key parts of mRNA vaccines—the mRNA itself and the lipid nanoparticles (LNPs) that deliver it—actively stimulate the immune system and work together to produce germinal centers and immune protection.

Although mRNA is chemically modified to reduce excessive inflammation and improve protein production, the study shows it is not completely "invisible" to the immune system. Instead, the mRNA induces low but biologically meaningful levels oftype I interferons, immune signals that help guide helper T cells into a form that supports strong antibody responses.

At the same time, theLNPsactivate immune cells called dendritic cells and help position them in lymph nodes where they can effectively instruct T cells to provide helper signals for B cells.

Led by Michela Locci, Ph.D., an associate professor of microbiology, the researchers also found that another immune signal, IL-1, plays a critical and independent role in shaping these responses. Together, these signals promote the formation of germinal centers, which are crucial for producing high-quality antibodies and establishing long-lived immune memory.

By uncovering how mRNA and LNP components act as built-in immune stimulators, this work provides important insights that could help scientists design even more effective mRNA vaccines in the future.

More information Diana Castaño et al, Distinct components of mRNA vaccines cooperate to instruct efficient germinal center responses, Cell (2025). DOI: 10.1016/j.cell.2025.11.023 Journal information: Cell