Aggregate content influences the Th1/Th2 immune response to influenza vaccine: evidence from a mouse model

During the 2000-2001 season, a newly identified oculo-respiratory syndrome (ORS) was detected across Canada as an adverse effect to one influenza vaccine. The implicated vaccine contained a higher than expected proportion of unsplit and aggregated influenza virions. Clinical and epidemiologic features of ORS were suggestive of type 2-like influences on the immune response. We hypothesized that the implicated vaccine from the 2000-2001 season would induce greater Th2-like polarization relative to the non-implicated vaccine from the same season. Three groups consisting of eight mice each were either immunized with implicated vaccine, immunized with non-implicated vaccine or not immunized. Antigen-specific cellular responses were characterized based on the balance of Th2 (IL-4, IL-5) and Th1 (IFN-gamma) cytokines in vitro. We confirm that vaccine aggregates deviate the immune response to a greater Th2 cytokine pattern with potential implications for vaccine screening, safety, and efficacy.