Safety and immunogenicity of BNT162b2 vaccine in children with acute leukaemia: results and perspectives of an open-label, two-centre, phase 1/2 trial with dose finding study

Background . COVID-19 can be severe in children with acute leukaemia (AL), significantly delaying chemotherapy. This is the first study to address the safety and immunogenicity of BNT162b2 in children with AL. Methods: The PACIFIC trial ( NCT04969601 ) was a phase 1/2 dose-finding study in children aged <15 years with AL and their siblings. Two doses of BNT162b2 vaccine were administered 21 days apart. The co-primary endpoints were safety, assessed by dose-limiting toxicity, and humoral immunogenicity, defined by an anti-Spike IgG titer ≥260 BAU/ml one month after the second injection. A third dose of vaccine was administered to children with an anti-Spike IgG titer <260 BAU/ml. Humoral and cellular immune responses were assessed for 12 months after the first vaccine injection. Results: Sixty-one patients and 15 siblings were included. No toxicity was observed during dose escalation. Thus, 44/53 children received the 30 μg vaccine dose. Two months after the first injection, the humoral response was lower in patients than siblings (52 % vs 100 %, p < 0.001), whereas the T-cell response was similar in the two groups (80 % versus 100 %, p = 0.1). A significant humoral response was observed in 43 % of patients after the third dose. Both humoral and Covid-19-specific T-cell responses persisted for at least one year after vaccination. No severe Covid-19 occurred during the study. Conclusions: Vaccination of children with acute leukaemia with adult doses (30 μg) of BNT162b2 is well tolerated and results in significant T-cell response children with AL, even during chemotherapy. As doses of 10 μg is currently recommended for children, these results support the value of increasing vaccine doses in immunocompromised patients. • COVID-19 can be severe in children with acute leukaemia, often causing delays in chemotherapy. • Two adult doses of BNT162b2 are well tolerated and induce strong T-cell responses, even during chemotherapy • Results support increasing COVID-19 vaccine doses in severely immunocompromised children instead of 10 μg doses. • Strong T-cell responses from mRNA vaccines may aid protection and future anti-infectious or anti-tumor strategies.