Rituximab‐to‐vaccine interval on SARS‐CoV‐2 immunogenicity in children: The potential role of prior natural infection

Abstract

AbstractBackgroundTreatment with anti‐CD20 antibodies (rituximab) is used in both adults and children to treat various autoimmune and oncological diseases. Rituximab depletes B CD20+ cells and, thereby, antibody response to vaccines. This study aimed to examine the antibody response to mRNA‐based COVID‐19 vaccines in children aged 5–18 years undergoing rituximab treatment compared to healthy matched children.MethodsBetween 31 January and 18 July 2022, we conducted a prospective observational study at the Geneva University Hospitals, enrolling children aged 5–18 years under rituximab treatment who had received two mRNA‐based SARS‐CoV‐2 vaccine doses. Controls were healthy volunteers with no significant medical conditions. Exclusion criteria included a recent SARS‐CoV‐2 infection. Blood samples were collected at day 60 (±30) and day 270 (±90) after the second vaccination.ResultsThe rituximab‐treated group exhibited significantly lower levels of antibodies specific to the anti‐receptor binding domain (RBD) of the SARS‐CoV‐2 spike (S) protein than healthy controls at 60 (±30) days after the second vaccine dose (geometric mean concentration: 868.3 IU/mL in patients and 11,393 IU/mL in controls; p = .008). However, patients with a rituximab‐to‐vaccine interval shorter than 6 months and with evidence of a past infection (based on positive anti‐N antibody levels) had a high level of anti‐RBD antibodies.ConclusionA past infection with SARS‐CoV‐2 may induce anti‐RBD‐specific memory B cells that can be re‐activated by SARS‐CoV‐2 vaccination, even after rituximab‐induced B‐cell depletion. This suggests that it is possible to vaccinate earlier than 6 months after rituximab to develop a good antibody response, especially in the case of past SARS‐CoV‐2 infection.