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, were infected with a 0.1 LD50 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+ CTL activity (P < 0.08--0.001) and IFN-gamma 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-gamma production among old mice (35 and 12,000 times, respectively). These results demonstrate that MPL stimulates CTL and Th1 cytokines (IFN-gamma) in aged mice and may serve to reverse age-related CD8+ CTL deficiency and reduce severe influenza disease in elderly human populations.
Mbawuike
I N
IN
Acute Viral Respiratory Disease Unit, Influenza Research Center, Baylor College of Medicine, Houston, Texas 77030-3498, USA.
Acuna
C
C
Caballero
D
D
Pham-Nguyen
K
K
Gilbert
B
B
Petribon
P
P
Harmon
M
M
D000276:Adjuvants, Immunologic; D000375:Aging; D000818:Animals; D004195:Disease Models, Animal; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000473:pathology / Q000821:virology; D007371:Interferon-gamma / Q000276:immunology*; D008050:Lipid A / Q000031:analogs & derivatives* / Q000276:immunology; D008081:Liposomes; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D015395:Histocompatibility Antigens Class I; D007252:Influenza Vaccines; D008050:Lipid A; D008081:Liposomes; D007371:Interferon-gamma; C048436:monophosphoryl lipid A