Sex and age differences in antibody responses to seasonal influenza vaccination are mediated by estrogenic upregulation of NF-κB and TNF signaling in B cells.

Estrogen-driven upregulation of NF-κB and TNF signaling in B cells mediates sex differences in influenza vaccine responses in young adults.

• Why it matters: Understanding the biological basis of sex differences in vaccine responses can improve vaccination strategies and address disparities, especially as these differences diminish with age.
• What they did: The study analyzed humoral immune responses in young and old adults, using antibody titers, B cell profiling, machine learning, single-cell RNA sequencing, and hormone treatments to investigate sex and age effects on vaccine-induced immunity.
• The result: Young adult females showed greater antibody responses linked to estrogenic activity and NF-κB/TNF pathway upregulation in B cells, with estrogen signaling identified as a key factor, while these differences were reduced in older adults.