REVERSAL OF AGE-RELATED DEFICIENT INFLUENZA VIRUS-SPECIFIC CTL RESPONSES AND IFN-GAMMA PRODUCTION BY MONOPHOSPHORYL LIPID-A

Old and young Balb/c mice, 24-26 and 2-4 months old, respectively, wer e infected with a 0.1 LD(50) of 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(+) CT L activity (P < 0.08-0.001) and IFN-gamma production (0.1-0.008) measu red on Days 8, 12, and 17 were significantly lower among old mice than among young mice. Coadministration of liposomal influenza vaccine wit h monophosphoryl lipid A (MPL) resulted in enhanced CD8(+) CTL respons e and IFN-gamma production among old mice (35 and 12,000 times, respec tively). These results demonstrate that MPL stimulates CTL and Th1 cyt okines (IFN-gamma) in aged mice and may serve to reverse age-related C D8(+) CTL deficiency and reduce severe influenza disease in elderly hu man populations. (C) 1996 Academic Press, Inc.