ANTIBODY PREVENTS THE ESTABLISHMENT OF PERSISTENT ARENAVIRUS INFECTION IN SYNERGY WITH ENDOGENOUS T-CELLS

A cardinal feature of the biology of lymphocytic choriomeningitis viru s (LCMV) is its ability to establish persistent infections in mice, Pe rsistence is usually established by infection of the mouse during the in utero or neonatal period. Susceptibility can be extended to the adu lt by treatment with immunosuppressive agents or by infection with imm unosuppressive strains of LCMV. In this study we investigated the capa city of passively acquired anti-LCMV antibodies to prevent the establi shment 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 withst ood Challenge doses of up to 400 PFU without becoming persistently inf ected. To establish that maternal antibody alone and not maternally de rived T cells provided this protection, nonimmune mothers were infused with monoclonal anti LCMV neutralizing antibodies within 24 h after d elivering their pups. Pups nursing on these passively immunized mother s were resistant to persistent LCMV infection. The establishment of pe rsistence in adult BALB/c mice by the immunosuppressive, macrophage-tr opic LCMV variant, clone 13 was also prevented by prophylactic treatme nt with anti-LCMV monoclonal antibodies, However, the protection affor ded by passively acquired antibody was found to be incomplete if the r ecipients lacked functional CD8(+) T cells. While 65% of neonatal athy mic (nu/nu) mice nursed by immune nu/+ dams resisted low-dose viral ch allenge (25 PFU), the majority of nude pups challenged with high doses of virus (100 PFU) became persistently infected. Also, protection was incomplete in beta(2)-microglobulin knockout mice, which lack functio nal CD8(+) T cells, suggesting that a cooperative effect was exerted b y the combination of neutralizing antibody and endogenous T cells. The se results indicate that antibodies provide an effective barrier to th e establishment of persistent infections in immunocompetent mice and r eaffirm that vaccines which induce strong humoral responses may provid e efficient protection against arenavirus infections.