COVID-19 boosters restore virus-specific immune responses in kidney transplant recipients unresponsive to primary vaccination.

Kidney transplant recipients (KTRs) often exhibit impaired immune responses to vaccination, necessitating multiple doses to obtain sufficient protection from severe disease. This study compared immunological mechanisms underlying the vaccine-induced response between KTRs who responded to primary vaccination (primary responders) and those who only responded to a booster vaccination (booster responders). Humoral immune responses, including binding and Fc-mediated functionalities, and T cell responses, were generally comparable in primary and booster responders. More in-depth analyses revealed that booster responders had an expanded memory B cell pool and stronger omicron BA.1 neutralization, while primary responders had more IL-21-producing T cells and a distinct SARS-CoV-2-specific CD4 T cell phenotype. Principal component analysis demonstrated that booster responders exhibited a more refined immune network integration. These results suggest that the delayed immune response of booster responders is not functionally impaired and that repeated vaccination is an effective strategy to achieve adequate protection in this population.