Influenza virus specific CD8⁺ T cells exacerbate infection following high dose influenza challenge of aged mice

Influenza viruses cause severe illnesses and death, mainly in the aged population. Protection afforded by licensed vaccines through subtype-specific neutralizing antibodies is incomplete, especially when the vaccine antigens fail to closely match those of the circulating viral strains. Efforts are underway to generate a so-called universal influenza vaccine expressing conserved viral sequences that induce broad protection to multiple strains of influenza virus through the induction of CD8⁺ T cells. Here we assess the effect of a potent antiviral CD8⁺ T cell response on influenza virus infection of young and aged mice. Our results show that CD8⁺ T cell-inducing vaccines can provide some protection to young mice, but they exacerbate influenza virus-associated disease in aged mice, causing extensive lung pathology and death.