Cutting edge: Long-term B cell memory in humans after smallpox vaccination

Memory B cells are a central component of humoral immunity, and yet little is known about their longevity in humans. Immune memory after smallpox vaccination (Dry Vax) is a valuable benchmark for understanding the longevity of B cell memory in the absence of re-exposure to If Ag. In this study, we demonstrate that smallpox vaccine specific memory B cells last for >50 years in immunized individuals. Virus-specific memory B celb initially declined postimmunization, but then reached a plateau similar to 10-fold lower than peak and were stably maintained for >50 years after vaccination at a frequency of similar to 0.1% of total circulating IgG(+) B cells. These persisting memory B cells were functional and able to mount a robust anamnestic Ab response upon revaccination. Additionally, virus-specific CD4(+) T cells were detected decades after vaccination. These data show that immunological memory to Dry Vax vaccine is long-lived and may contribute to protection against smallpox.