Reversal of Age-Related Deficient Influenza Virus-Specific CTL Responses and IFN-γ Production by Monophosphoryl Lipid A

Old and young Balb/c mice, 24–26 and 2–4 months old, respectively, were infected with a 0.1 LD50of influenza A/Taiwan/1/86 (A/H1N1) virus by small particle aerosol. Lung virus titers were determined 4, 6, 8, 12, and 17 days later. Old mice had significantly higher virus titers than young mice (P< 0.05–0.0001) and shed virus up to Day 17, while young mice were free of virus by Day 12. Splenic MHC class I CD8+CTL activity (P< 0.08–0.001) and IFN-γ production (0.1–0.008) measured on Days 8, 12, and 17 were significantly lower among old mice than among young mice. Coadministration of liposomal influenza vaccine with monophosphoryl lipid A (MPL) resulted in enhanced CD8+CTL response and IFN-γ production among old mice (35 and 12,000 times, respectively). These results demonstrate that MPL stimulates CTL and Th1 cytokines (IFN-γ) in aged mice and may serve to reverse age-related CD8+CTL deficiency and reduce severe influenza disease in elderly human populations.