The impact of ethnicity on longitudinal humoral and cellular immune responses to SARS-CoV-2 booster vaccination

Ethnic differences in SARS-CoV‑2 vaccine immunogenicity have been reported after primary vaccination, but it remains unclear whether these disparities persist following booster doses or whether patterns of immune boosting and waning differ across ethnic groups. In this longitudinal study of healthcare workers enrolled in the BE‑DIRECT cohort, we evaluated humoral and cellular immune responses before booster vaccination, 3-4 weeks afterwards, and at approximately six months. Anti‑spike and neutralising antibodies, as well as T‑cell ELISpot responses to spike peptides, were quantified, and changes across boosting and waning phases were examined using multivariable regression adjusting for demographic factors, vaccine regimen, prior infection and baseline immune measures. South Asian participants demonstrated substantially higher post‑booster anti‑spike titres than White participants, although titres converged by six months. After adjustment, South Asian individuals exhibited greater increases in total anti-spike and neutralising antibody titres, while decline in antibody titres between post-booster and six-month post-booster sampling points were similar across ethnic groups. T‑cell responses during the boosting phase did not differ, but decline of S2‑specific and overall spike‑specific T‑cell responses between post-booster and six-month post-booster sampling points occurred more slowly in South Asians. These findings indicate that South Asian healthcare workers mount stronger early booster‑induced antibody responses and exhibit more sustained T‑cell immunity, highlighting the need to understand underlying mechanisms and implications for vaccine effectiveness.