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

Area of Science:

• Immunology
• Vaccinology

Background:

• Memory B cells are crucial for adaptive immunity, but their longevity in humans remains incompletely understood.
• Smallpox vaccination provides a unique model to study long-term B cell memory due to its historical widespread use and the absence of continuous antigen exposure.

Purpose of the Study:

• To investigate the duration and functionality of memory B cells following smallpox vaccination (DryVax) in humans.

Main Methods:

• Quantification of smallpox vaccine-specific memory B cells in peripheral blood of individuals vaccinated decades prior.
• Assessment of the functional capacity of these memory B cells to elicit an antibody response upon revaccination.
• Detection of virus-specific CD4(+) T cells post-vaccination.

Main Results:

• Smallpox vaccine-specific memory B cells were detected at stable levels (>50 years post-vaccination), representing approximately 0.1% of circulating IgG(+) B cells.
• These long-lived memory B cells remained functional, mounting a significant anamnestic antibody response after revaccination.
• Virus-specific CD4(+) T cells were also identified decades after initial immunization.

Conclusions:

• Immunological memory to the smallpox vaccine is remarkably long-lived in humans.
• Persisting functional memory B cells and T cells likely contribute to sustained protection against smallpox infection.