Weaker humoral Immune Response to Tetanus Toxoid in Mice Receiving Beta-Lactam/ Ceftriaxone Treatment

<ns3:p>Context The human endonuclease Artemis, required for immunoglobulin rearrangements of V(D)J segments in B cells and thereby contributing to the adaptive immune response, belongs to the metallo-β-lactamase enzyme superfamily. β-lactam antibiotics, including ceftriaxone, are widely used in clinical practice and display strong affinity for β-lactamase catalytic sites. In vitro, ceftriaxone has been shown to block the activity of Artemis. Based on these structural similarities, the hypothesis according to which certain β-lactams could inhibit Artemis and therefore the immune response was previously proposed by our teams. This study aimed to determine in vivo whether ceftriaxone exposure alters vaccine-induced humoral immunity. Methods To explore the hypothesis put forward above, we developed an animal model to evaluate the antibody immune response to tetanus toxin induced by a diphtheria–tetanus–poliomyelelitis (DTP) vaccine in the presence or absence of ceftriaxone. Male BALB/c mice were vaccinated either before or after a five-day intraperitoneal ceftriaxone treatment; control groups received isotonic saline. The mice immune response to vaccine was quantified by measuring interactions with specific antigens using immunochromatographic tests, enabling longitudinal assessment of anti-tetanus toxoid antibodies. Results We report the first experimental evidence of a specific weakening of vaccine-induced immune response in animals receiving ceftriaxone, with significantly reduced anti-tetanus antibody levels when vaccination followed antibiotic exposure. The response remained efficient in animals receiving isotonic saline treatment as control, and in mice vaccinated prior to ceftriaxone administration. Conclusions These results confirm our hypothesis that the immune response to tetanus toxin is impaired and that a refractory period for humoral immunity may be caused by the inhibition of Artemis by ceftriaxone. This work highlights a clinically relevant interaction between β-lactam antibiotics and adaptive immune responses.</ns3:p>