A cardinal feature of the biology of lymphocytic choriomeningitis virus (LCMV) is its ability to establish
persistent infections in mice. Persistence is usually established by
infection of the mouse during the in utero or neonatal period. Susceptibility can be extended to the adult by treatment with
immunosuppressive agents or by
infection with immunosuppressive strains of LCMV. In this study we investigated the capacity of passively acquired anti-LCMV
antibodies to prevent the establishment of persistence in both neonatal and adult mice. Suckling BALB/c mouse pups nursed by mothers immunized against LCMV before pregnancy had higher survival rates following
infection than controls and withstood challenge doses of up to 400 PFU without becoming persistently infected. To establish that maternal antibody alone and not maternally derived T cells provided this protection, nonimmune mothers were infused with monoclonal anti-LCMV
neutralizing antibodies within 24 h after delivering their pups. Pups nursing on these passively immunized mothers were resistant to persistent LCMV
infection. The establishment of persistence in adult BALB/c mice by the immunosuppressive, macrophage-tropic LCMV variant, clone 13 was also prevented by prophylactic treatment with anti-LCMV
monoclonal antibodies. However, the protection afforded by passively acquired antibody was found to be incomplete if the recipients lacked functional CD8+ T cells. While 65% of neonatal athymic (nu/nu) mice nursed by immune nu/+ dams resisted low-dose viral challenge (25 PFU), the majority of nude pups challenged with high doses of virus (100 PFU) became persistently infected. Also, protection was incomplete in beta2-microglobulin knockout mice, which lack functional CD8+ T cells, suggesting that a cooperative effect was exerted by the combination of
neutralizing antibody and endogenous T cells. These results indicate that
antibodies provide an effective barrier to the establishment of
persistent infections in immunocompetent mice and reaffirm that
vaccines which induce strong humoral responses may provide efficient protection against
arenavirus infections.