title: The manufacturing process should remain the focus for severe febrile reactions in children administered an Australian inactivated influenza vaccine during 2010.
abstract: Influenza vaccine safety is an ongoing issue. In 2010, inactivated trivalent influenza vaccines (TIVs), Fluvax(®) and Fluvax Junior(®) manufactured by CSL Biotherapies ('CSL'), Parkville, Australia, were associated with a marked increase in febrile seizures (FS) in children <5 years old. Extensive investigations initially failed to identify a root cause. The company's researchers recently published two papers outlining their latest findings. Cytokine responses to TIV were measured in paediatric whole blood assays (WBA); NF-κB activation was assessed using a HEK293 cell line reporter assay. CSL suggest that the combination of new influenza strains (H1N1 A/California/7/2009 and B/Brisbane/60/2008), increased complexes of viral RNA and lipid in the vaccine, and inherent sensitivities of some children <5 years old caused elevated inflammatory responses resulting in FS. Whilst the papers provide insight into pathogenesis, much remains unclear. The WBA were from only 10 'healthy' children, potentially affecting generalisability of the results and reliability of these in vitro tests in assessing future influenza vaccine safety. Increased fever rates (without FS) found in CSL TIV studies between 2005 and 2010 suggest a long-standing contribution to reactogenicity from the manufacturing process. More detailed comparisons with non-CSL vaccines would have helped elucidate the relative contribution of patient/strain factors and the manufacturing process. The focus remains on manufacturing process differences as the key causative factor of elevated febrile responses. Studies underway, of modified vaccines in young children, will determine whether reactogenicity issues have been successfully addressed and whether CSL TIV can be relicensed in children <5 years of age.
authors.affiliation: National Centre for Immunisation Research and Surveillance, The Children's Hospital at Westmead, Sydney, NSW, Australia.|Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Jean
authors.initials: J
authors.lastname: Li-Kim-Moy
authors.affiliation: National Centre for Immunisation Research and Surveillance, The Children's Hospital at Westmead, Sydney, NSW, Australia.|Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.|The Children's Hospital at Westmead, Sydney, NSW, Australia.|Marie Bashir Institute for Infectious Diseases & Biosecurity, University of Sydney, Sydney, NSW, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Booy
mesh_terms: D001315:Australia; D002675:Child, Preschool; D057809:HEK293 Cells; D006801:Humans; D007223:Infant; D007252:Influenza Vaccines / Q000009:adverse effects* / Q000096:biosynthesis*; D061214:Patient Safety; D011358:Product Surveillance, Postmarketing; D003294:Seizures, Febrile / Q000139:chemically induced*
chemical_list: D007252:Influenza Vaccines
keywords: Adverse events; CSL; febrile seizures; fever; influenza vaccine; safety