Longitudinal Innate and Heterologous Adaptive Immune Responses to SARS-CoV-2 JN.1 in Transplant Recipients With Prior Omicron Infection: Limited Neutralization but Robust CD4+ T-Cell Activity.

BACKGROUND

Solid organ transplant (SOT) recipients are at increased risk for severe COVID-19 and often exhibit reduced vaccine efficacy due to chronic immunosuppression. As new SARS-CoV-2 variants emerge, understanding immune responses following natural infection remains critical for informing protection strategies in this vulnerable population. We conducted a longitudinal study of SOT recipients who had recovered from Omicron BA.1 or BA.2 infection, evaluating immune responses to the JN.1 subvariant at 4-6 weeks and 1 year postinfection.

METHODS

Neutralizing antibodies to JN.1 were measured using a pseudovirus neutralization assay, and JN.1-specific T-cell responses were assessed by flow cytometry. Frequencies of bulk T-cells and innate immune cells, identified via flow cytometry, and their correlation with adaptive responses were also analyzed.

RESULTS

At 4-6 weeks, 30% of participants had detectable JN.1-neutralizing antibodies, rising to 43% at one year, although titers remained low. In contrast, CD4⁺ T-cell responses were robust and detected in 75%-83% of participants at 4-6 weeks, increasing to 75%-93% by 1 year. CD8⁺ T-cell responses were observed less frequently. Exploratory correlations between innate and bulk T-cell subsets with heterologous adaptive immune responses were investigated but did not reveal statistically significant relationships.

CONCLUSION

These findings offer important insights into the durability and breadth of immunity following natural infection in immunocompromised transplant recipients. While heterologous neutralizing antibodies were limited, sustained CD4+ T-cell responses may help mitigate severe disease following exposure to JN.1-derived variants, which continue to dominate the SARS-CoV-2 landscape.