New in Nature Immunology: Platelets and the Secret to Lasting Immunity

Vaccines work by training your immune system to recognize and fight off dangerous viruses. But why do some vaccines provide years of protection while others fade fast? In a new study, led by Bali Pulendran and Mario Cortese at Stanford, we uncovered an unexpected player in the durability of vaccine responses: platelets, best known for there central role in blood clotting.

In our study, we used a systems vaccinology approach to analyze immune responses in people who received an H5N1 avian flu vaccine, with and without the AS03 adjuvant. When we looked at gene activity in the blood, we found something unexpected—a signature related to platelets and cell adhesion appeared just seven days after vaccination. Even more surprising? This signature predicted how long antibody responses would last.

That got us thinking: Could platelets be actively shaping vaccine durability? To test this, we focused on megakaryocytes, the bone marrow cells that produce platelets. When we stimulated them using thrombopoietin (TPO)—a hormone that drives platelet production—we saw that vaccine-induced antibodies stuck around much longer. Digging deeper, we found that TPO-activated megakaryocytes support plasma cell survival through specialized molecular interactions, including integrin β1/β2 signaling, APRIL, and the MIF–CD74 axis. Plasma cells are the factories that keep producing antibodies, so their survival is crucial for long-term immunity.

To see if this finding extended beyond just one vaccine, we built a machine-learning model based on the platelet-associated signature. When we tested it across six different vaccines from seven independent trials, the pattern held up—suggesting this could be a shared mechanism for vaccine durability.

Summary of proposed mechanism. From Cortese et al., Nature Immunology, 2025.

These findings raise exciting possibilities. Could targeting platelets or megakaryocytes help design longer-lasting vaccines? Could TPO or similar strategies boost immunity in vulnerable populations? There’s still much to explore, but one thing is clear: platelets are doing more than we ever expected in shaping immune memory.