Immune responses following sequential mRNA booster doses targeting the SARS-CoV-2 omicron variants in immunocompromised individuals – A 3.5-year follow-up

Immunocompromised individuals mount suboptimal responses to COVID-19 vaccines, necessitating additional booster dose recommendations. However, long-term data on humoral and T-cell mediated immunity following sequential doses in this population remain limited. We followed 24 individuals living with chronic kidney disease ( n = 10) or rheumatological disease ( n = 14) with diverse COVID-19 vaccination and infection history for up to 3.5 years. We assessed humoral and cellular immune responses before and after sequential original/BA.4–5 and JN.1 variant-adapted booster doses. Binding and neutralizing antibodies (NAbs) and T-cell responses to wild-type, BA.5, XBB.1.5, and JN.1 were analyzed before and one month after vaccination and compared to healthy controls ( n = 13) who had received three doses of the original vaccine. The BA.4–5 booster vaccination increased NAb response rates to 90–100% (wild-type), 80–100% (BA.5.1), 71–86% (XBB.1.5), and 43–71% (JN.1). The JN.1 booster further increased NAb levels against JN.1 by 5.3-fold and raised response rates to 80–100%. T-cell responses were detected across all variants, and remained comparable to healthy controls, even in patients with lower or waning antibody levels. However, additional booster doses did not further augment T-cell responses. Sequential administration of variant-adapted COVID-19 boosters broadened neutralizing activity against Omicron subvariants, although it did not further elevate antibody levels beyond prior doses. T-cell responses remained stable and unenhanced by additional boosting, indicating potential for durable cellular protection despite low or waning antibody levels.