Role of antibodies in a primarily T cell-controlled viral infection model in mice

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Control of non-cytopathic viruses such as hepatitis C virus (HCV) in humans or lymphocytic choriomenigitis virus (LCMV) in mice is primarily mediated by CD8 T cells. Humoral immunity is considered to be of minor importance since neutralizing antibodies appear only late and are of low titer. In our preliminary project-specific work, we analyzed mice with impaired antibody formation and surprisingly found that low dose infection with a rapidly replicating LCMV strain led to T cell exhaustion and virus persistence in contrast to wild-type mice that cleared the infection. Thus, natural or induced LCMV-specific antibodies present at early time points after infection may lower viral replication and assist in T cell-mediated clearance despite lack of neutralization activity. The overall aim of this project is to provide direct evidence for this hypothesis and to clarify the mechanisms of how non-neutralizing LCMV-specific antibodies decrease viral load and prevent T cell exhaustion. The work schedule involves adoptive transfer experiments with antibodies and B cells into antibody-deficient recipient mice followed by LCMV infection and subsequent examination of viral clearance and T cell activity. In addition, a panel of LCMV-specific monoclonal antibodies carrying different isotypes will be generated and their mode of action will be determined.