Modification of the vaccine manufacturing process improves the pyrogenicity profile of inactivated influenza vaccines in young children.

Abstract

BACKGROUND\nThere were increased reports of fevers and febrile reactions in young children (particularly children aged <5\u202fyears) receiving the Seqirus/CSL Southern Hemisphere 2010 trivalent inactivated influenza vaccine (IIV3). Modifying the vaccine manufacturing process by increasing the minimum concentration of splitting agent (sodium taurodeoxycholate [TDOC]) from 0.5% w/v to 1.5% w/v for all strains resolved this issue. The current analysis compared fever rates in three pediatric studies of Seqirus IIV3 (S-IIV3) or quadrivalent inactivated influenza vaccine (S-IIV4), prepared using the modified manufacturing process, with fever rates in three pediatric studies of historical (pre-2010) IIV3 formulations. The historical IIV3 formulations, S-IIV3, and S-IIV4 had 0/3, 2/3, and 4/4 vaccine strains split at 1.5% TDOC, respectively.\n\n\nMETHODS\nFor each study, fever rates (any grade and severe) were determined for the following age subgroups (as applicable), using the fever intensity grading system used in the S-IIV3/S-IIV4 studies: 6\u202fmonths to <3\u202fyears; 3 to <5\u202fyears; 5 to <9\u202fyears; and 9 to <18\u202fyears.\n\n\nRESULTS\nFor each age subgroup, the any grade and severe fever rates were lower in the S-IIV3/S-IIV4 studies than in the historical IIV3 formulation studies, with the greatest differences in fever rates observed in the youngest age groups. In the 6\u202fmonths to <3\u202fyears group, the any grade fever rate was 7.0% (severe fever: 2.5%) in one S-IIV4 study compared with 38.7% to 40.0% (severe fever: 9.6% to 17.8%) in the historical IIV3 formulation studies. In the 3 to <5\u202fyears subgroup, the any grade fever rate was 4.9% (severe fever: 1.2%) in one S-IIV4 study compared with 34.1% to 36.0% (severe fever: 6.3% to 16.5%) in the historical IIV3 formulation studies.\n\n\nCONCLUSION\nThis analysis provides clinical evidence that the modified manufacturing process improved the fever profile across all pediatric age groups, in particular, in children aged <5\u202fyears.