Memory B cell development elicited by mRNA booster vaccinations in the elderly

Area of Science:

• Immunology
• Virology
• Gerontology

Background:

• Elderly individuals exhibit increased vulnerability to severe SARS-CoV-2 outcomes despite mRNA vaccination.
• Understanding age-related differences in immune memory is critical for optimizing vaccine strategies.

Purpose of the Study:

• To compare SARS-CoV-2-specific memory B cell responses in elderly versus younger individuals following mRNA booster vaccination.
• To investigate the characteristics and functional capacity of memory B cells and antibodies in different age groups.

Main Methods:

• Comparative analysis of memory B cell populations in elderly and younger cohorts post-mRNA booster.
• Assessment of plasma neutralizing antibody potency and breadth.
• Antibody sequencing to analyze B cell repertoire diversity and epitope targeting.

Main Results:

• Elderly individuals showed a lower absolute number of SARS-CoV-2-specific memory B cells compared to younger individuals.
• The memory B cell compartments in the elderly were more clonal and less diverse.
• Antibodies from the elderly preferentially targeted the ACE2-binding site, while younger individuals' antibodies targeted more conserved epitopes.

Conclusions:

• Diminished vaccine protection against severe disease in the elderly is linked to a reduced number of antigen-specific memory B cells with altered antibody repertoires.
• Despite repertoire differences, individual memory antibodies demonstrated similar neutralizing activity against SARS-CoV-2 variants in both age groups.