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February 26, 2026Vaccine0 citationsOpen Access

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

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NENina EkströmOLOona LiedesSVSaimi Vara

Key Points

  • To assess the immune responses of immunocompromised individuals following sequential mRNA booster doses targeting SARS-CoV-2 omicron variants over 3.5 years.
  • Monitored 24 immunocompromised individuals with chronic kidney or rheumatological diseases for 3.5 years.
  • Evaluated humoral and cellular immune responses pre- and post-booster doses of original/BA.4–5 and JN.1 variants.
  • Compared responses to healthy controls who received three doses of the original vaccine.
  • BA.4–5 booster increased neutralizing antibody rates to 90–100% (wild-type) and 80–100% (BA.5.1).
  • JN.1 booster improved NAb levels against JN.1 by 5.3-fold, raising response rates to 80–100%.
  • T-cell responses were maintained across all variants and compared favorably to healthy controls despite lower antibody levels.

Abstract

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.

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Cite This Study

Ekström et al. (2026) studied this question.

synapsesocial.com/papers/699fe32295ddcd3a253e6c00https://doi.org/10.1016/j.vaccine.2026.128347
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