Effect of prophylactic administration of antipyretics on the immune response to pneumococcal conjugate vaccines in children: a systematic review

Background Prophylactic administration of antipyretics at the time of immunization seems to decrease some side effects, however reduced immune responses have been reported in some studies. This systematic review aimed to investigate the effect of prophylactic use of antipyretics on the immune response following administration of pneumococcal conjugate vaccines (PCVs). Methods A systematic review of randomized controlled trials and observational studies concerning the immune response to PCVs after antipyretic administration was performed up to November 2020 in the electronic databases of Pubmed and Scopus. Results Of the 3956 citations retrieved, a total of 5 randomized control trials including 2775 children were included in the review. Included studies were referred to PCV10 (3 studies), PCV7 and PCV13 (one study each). The prophylactic administration of paracetamol decreased the immune response to certain pneumococcal serotypes in all included studies. The effect was more evident following primary vaccination and with immediate administration of paracetamol. Despite the reductions in antibody geometric mean concentrations, a robust memory response was observed following the booster dose. Besides, antibody titers remained above protective levels in 88-100% of participants. The use of ibuprofen, that was evaluated in two studies, did not seem to affect the immunogenicity of PCVs . Conclusion Although the reviewed studies had significant heterogeneity in design, paracetamol administration seems to affect the immune response for certain serotypes. The clinical significance of reduced immunogenicity especially before booster dose needs further investigation.