Atypical B cells and impaired SARS-CoV-2 neutralization following heterologous vaccination in the elderly.

Suboptimal responses to a primary vaccination course have been reported in the elderly, but there is little information regarding the impact of age on responses to booster third doses. Here, we show that individuals 70 years or older (median age 73, range 70–75) who received a primary two-dose schedule with AZD1222 and booster third dose with mRNA vaccine achieve significantly lower neutralizing antibody responses against SARS-CoV-2 spike pseudotyped virus compared with those younger than 70 (median age 66, range 54–69) at 1 month post booster. Impaired neutralization potency and breadth post third dose in the elderly is associated with circulating "atypical" spike-specific B cells expressing CD11c and FCRL5. However, when considering individuals who received three doses of mRNA vaccine, we did not observe differences in neutralization or enrichment in atypical B cells. This work highlights the finding that AdV and mRNA COVID-19 vaccine formats differentially instruct the memory B cell response. [Display omitted] • Two doses AZD1222 and BNT162b2 dose 3 show lower neutralization in older individuals • Reduced neutralization is not related to binding antibody or spike-specific B cell frequency • Reduced neutralization associates with circulating "atypical" B cells in the elderly • T cell responses, especially IL-2 secretion, show age-associated impairment post dose 3 Ferreira et al. show that older individuals vaccinated with two doses of AZD1222 and a third dose with mRNA achieve lower neutralizing antibody responses against SARS-CoV-2 compared with younger individuals and associate with spike-specific atypical B cells. Age-related differences in serum neutralization are not observed following three mRNA vaccine doses. [ABSTRACT FROM AUTHOR]