Neutralizing Antibody and T-Cell Spike Targeted Responses Following Receipt of a Monovalent Omicron JN.1-Adapted mRNA COVID-19 Vaccine in Immunosuppressed and Healthy Individuals.

We evaluated homologous neutralizing antibody (NtAb) and T-cell responses after receipt of a JN.1-adapted mRNA vaccine in a mixed population comprising healthy controls (HC) (n = 15), end-stage chronic kidney disease (CKD) patients (n = 17), and allogeneic hematopoietic stem cell transplant recipients (allo-HCT) (n = 13). Most participants (42/45) were SARS-CoV-2-experienced at the time of immunological testing. JN.1-spike-binding NtAbs were measured with a vesicular stomatitis virus pseudotype-based neutralization assay, whereas interferon (IFN)-γ-producing spike-directed CD4 or CD8 T-cell frequencies were enumerated using flow cytometry for intracellular staining. All participants had detectable JN.1 NtAbs at baseline; overall, JN.1-NtAb levels increased in HC (median, ∼1 log; p < 0.001) and CKD patients (median, 0.8 log; p = 0.06) but not in allo-HCT (p = 0.10). JN.1-NtAb titers measured after vaccination were significantly higher in HC than in CKD and allo-HCT (p = 0.01). The number of participants exhibiting detectable JN.1 T-cell responses did not significantly increase following booster vaccination in any of the study groups. Likewise, receipt of the Omicron JN.1 vaccine failed to significantly boost SARS-CoV-2 JN.1 CD8 and CD4 T-cell frequencies in any study groups. Nevertheless, trends in JN.1 T-cell frequencies following the JN-1 booster varied widely on an individual basis. JN.1 T-cell frequencies following JN.1 vaccination were comparable across study groups. Our results could have implications for the development of vaccines for future SARS-CoV-2 variants and the optimization of booster vaccination policies in allogeneic hematopoietic transplant recipients and patients with end-stage chronic kidney diseases.