Adjuvant-attenuated symptom severity of influenza infections in vaccinated children

Background: Young children are at high risk for developing complications of influenza, as well as severe clinical presentation of disease. Vaccination provides direct protection and reduces symptom severity in breakthrough infections. We assessed whether adjuvanted trivalent seasonal influenza vaccine is associated with symptom severity in children who developed laboratory-confirmed influenza, as compared to children who received quadrivalent inactivated influenza. Methods: A cluster randomized controlled trial of influenza vaccines in Canadian Hutterite colonies was conducted from the 2016-2017 to the 2018-2019 influenza season. Children were vaccinated with either quadrivalent inactivated influenza vaccine (QIV), or the MF59 adjuvanted trivalent influenza vaccine (aTIV). We assessed children who developed PCR-confirmed influenza infection for symptom severity outcomes using multivariable generalized negative binomial regression. Results: Among vaccinated children, 49 infections were observed across 1779 person-days. Vaccine formulation (aTIV vs QIV) was not significantly associated with composite symptom outcomes, including total number of symptoms or total duration of symptom presentation (p > 0.05 for all outcomes). Receipt of aTIV vaccination was significantly associated with attenuation of fever, with an estimated 74% reduction in fever severity. In influenza A type infections, adjuvanted vaccination was significantly associated with reduced systemic symptoms (incidence rate ratios: 0.16, 95% confidence intervals: 0.03, 0.64, p = 0.01). No associations were observed between vaccine formulation and symptom severity in influenza B infections. Conclusions: In vaccinated children who develop an influenza infection, vaccine formulation was associated with attenuated fever severity, leading to reduced systemic symptoms. In influenza A infections, adjuvanted vaccination was significantly associated with reduced systemic symptoms. Conclusions: Clinical Trials Registry: NCT02871206.