Compromised antibody responses and memory lymphocyte formation to COVID-19 mRNA vaccination in children with acute lymphoblastic leukemia undergoing maintenance chemotherapy

COVID-19 mRNA vaccines, with 95% efficacy in the general population, have been shown to exhibit suboptimal effectiveness in hematological malignancy patients. Our previous published study revealed that COVID-19 vaccine responses were related to innate immune responses. In this study, we investigated the innate and adaptive immune responses to COVID-19 mRNA vaccines in children with acute lymphoblastic leukemia (ALL). We longitudinally investigated the innate immune responses to PRR-agonists stimulation and after vaccine injection, along with vaccine-induced anti-S antibodies, S-specific memory B and T cell responses in 13 ALL children who completed or were undergoing maintenance chemotherapy and 24 healthy controls. We found that both ALL groups had impaired dsDNA-induced cytotoxic NK cell activation while patients in maintenance therapy also showed decreased dsRNA-induced activation in those cells. After vaccination, ALL children with completed therapy demonstrated similar S-specific antibody responses and memory B cells as healthy controls. In patients with maintenance therapy, these responses were notably reduced, especially cross-protective antibodies. Both ALL groups exhibited lower S-specific CD8⁺ T cells, which correlated with weaker TLR9 responses. In conclusion, we discovered the compromised vaccine responses in ALL children, especially those in maintenance chemotherapy, highlighting the importance of improved COVID-19 vaccines for this special group of patients.