Immunogenicity and Safety of an MF59-adjuvanted Quadrivalent Seasonal Influenza Vaccine in Young Children at High Risk of Influenza-associated Complications: A Phase III, Randomized, Observer-blind, Multicenter Clinical Trial

Abstract

Background: Vaccination against seasonal influenza is recommended for all children with a history of medical conditions placing them at increased risk of influenza-associated complications. The immunogenicity and efficacy of conventional influenza vaccines among young children are suboptimal; one strategy to enhance these is adjuvantation. We present immunogenicity and safety data for an MF59-adjuvanted quadrivalent influenza vaccine (aIIV4) in healthy children and those at a high risk of influenza-associated complications, based on the results of a recently completed phase III study. Methods: Children 6 months to 5 years of age (N = 10,644) were enrolled. The study was conducted across northern hemisphere seasons 2013–2014 and 2014–2015. Subjects received either aIIV4 or a nonadjuvanted comparator influenza vaccine. Antibody responses were assessed by hemagglutination inhibition assay against vaccine and heterologous strains. Long-term antibody persistence was assessed (ClinicalTrials.gov: NCT01964989). Results: aIIV4 induced significantly higher antibody titers than nonadjuvanted vaccine in high-risk subjects. aIIV4 antibody responses were of similar magnitude in high-risk and healthy subjects. Incidence of solicited local and systemic adverse events (AEs) was slightly higher in aIIV4 than nonadjuvanted vaccinees, in both the healthy and high-risk groups. Incidence of unsolicited AEs, serious AEs and AEs of special interest were similar for adjuvanted and nonadjuvanted vaccinees in the healthy and high-risk groups. Conclusion: aIIV4 was more immunogenic than nonadjuvanted vaccine in both the healthy and high-risk study groups. The reactogenicity and safety profiles of aIIV4 and the nonadjuvanted vaccine were acceptable and similar in 6-month- to 5-year-old high-risk and healthy children.

“World in motion” – emulsion adjuvants rising to meet the pandemic challenges

“…MF59 adjuvant increased influenza vaccine efficacy from 43 to 89% in young children 40 and is an effective adjuvant for influenza vaccines in this population 41 . Phase III studies of MF59 quadrivalent seasonal influenza vaccines in young children have been completed in Europe 42 and are ongoing in the US (ClinicalTrials.gov Identifier: NCT01346592 43 ).…”

Cord Blood-Based Approach to Assess Candidate Vaccine Adjuvants Designed for Neonates and Infants

“…In this regard, because vaccine adjuvants enhance antigen recognition by host APCs, such as DCs, and thus contribute to the effective induction of protective acquired immunity [ 59 , 60 , 61 ], the development of vaccines for children must include appropriate adjuvants that efficiently activate the immature immune system. To date, various adjuvants (e.g., alum, chitosan, and MF59) have been developed and used in mice and humans [ 62 , 63 , 64 , 65 , 66 , 67 ], and some of them were tested in children [ 64 , 66 , 67 ]. Alum, salts of aluminum, is the classical adjuvant most often used in vaccines in humans.…”

“…MF59, a potent oil-in-water emulsion, has been developed and used as adjuvant for influenza vaccine and its safety and effectiveness confirmed in adult [ 65 ]. Recent studies also demonstrated that MF59 is effective and safe in young children 6–35 months as influenza vaccine adjuvant [ 66 , 67 ], whereas it needs further confirmation whether MF59 is safe and effective in children as a potent universal adjuvant for other vaccine antigens.…”