Effect of Rimantadine on Cytotoxic T Lymphocyte Responses and Immunity to Reinfection in Mice Infected with Influenza A Virus

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Abstract
Administration of rimantadine to mice via drinking water, following a prophylactic dose, reduced lung virus titers by >3 log10 plague-forming units (pfu)/ml but caused only marginal reductions in lung virus titers when therapy wasstarted 8 h after exposure to virus. Mice given rimantadine prophylactically plus therapeutically were resistant to rechallenge with virus at a dose equivalent to that used for the primary infection (SO pfu/mouse) but not to a high dose (1 × 105 pfu/mouse). VIrUS-neutralizing-antibody titers were reduced only by rimantadine treatment, which included prophylaxis, whereas the cytotoxic T lymphocyte (CTL) response was depressed by treatment givenwith or without prophylaxis.Miceinfected with rimantadine-resistant virus had no decrease in CTL or antibody responses when treated with rimantadine. Therefore, the depression in CTL and antibody responses associated with rimantadine treatment appears to bedue to a decrease in the amount of viral antigen available or interference with viral antigen processing and not to nonspecific immunosuppressive effects.