Antipyretic Effect on Immune Response to Flu Vaccination in Young Children

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Patient responses to the inactivated influenza vaccine were assessed using hemagglutination inhibition assays.
Patient responses to the inactivated influenza vaccine were assessed using hemagglutination inhibition assays.

The administration of antipyretics for the treatment of local discomfort and fever in young children following receipt of inactivated influenza vaccine (IIV) is not associated with any significant blunting of the immune response, according to the results of 2 consecutive randomized controlled trials ( identifiers: NCT01946594 and NCT02212990) published in Vaccine.

The 2 trials were conducted from October 2013 to March 2014 (the pilot study), and then from September 2014 to April 2015 and from September 2015 to March 2016 (the expanded study, which included combined data). In the randomized (1:1) controlled double-blind pilot study, treatment with acetaminophen vs placebo following IIV was compared. The expanded study included an open-label ibuprofen arm as well, with patients randomly assigned in a 3:3:2 ratio to acetaminophen, placebo, or ibuprofen.


During the course of the 3 influenza seasons evaluated in the pilot study and the 2 expanded studies, a total of 142 children were included. The participants, who received either a single IIV dose or the first of 2 recommended doses of IIV, were randomly assigned to either oral acetaminophen suspension (n=59) or placebo (n=59; double-blinded), or ibuprofen (n=24; open-label), immediately following IIV administration, then every 4 to 8 hours thereafter, for 24 hours. Blood samples from each patient were obtained at enrollment and 4 weeks after administration of the last recommended IIV dose.

Patient responses to IIV were assessed using hemagglutination inhibition (HAI) assays, which measured antibody titers against the influenza test strains. The primary study outcome was seroconversion postvaccination, denoted as an HAI titer ≥1.40 if the baseline titer was <1.10 or a 4-fold increase in HAI titer if the baseline titer was ≥1.10. Additional immunogenicity measures included seroprotection, as determined by an HAI titer ≥1.40, and the geometric mean titer at baseline and 1 month after the last IIV dose. All participants were monitored for the development of fever or other solicited symptoms on the day of and the day following IIV administration.

No significant differences were observed in seroconversion and postvaccination seroprotection between children in the different antipyretic groups and the placebo group with respect to the vaccine antigens included in IIV over the course of the 3 studies. The frequency of solicited symptoms, including fever, was similar between the treatment arms and the placebo arm. Furthermore, no statistically significant differences were reported in either baseline or follow-up geometric mean titers for any of the influenza strains between either of the treatment groups and the placebo group.

The investigators concluded that to further address the use of antipyretics as a preventive strategy among pediatric patients at risk for development of fever and possible febrile seizures following IIV, additional research is warranted.

Disclosures: Dr Walter reports financial relationships with bioCSL, GlaxoSmithKline, Merck, Novartis, Novavax, and Pfizer. 


Walter EB, Hornik CP, Grohskopf L, et al. The effect of antipyretics on immune response and fever following receipt of inactivated influenza vaccine in young children. Vaccine. 2017;35(48, Part B):6664-6671. 

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