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J. Virol., 01 1997, 755-758, Vol 71, No. 1
JR Baldridge, TS McGraw, A Paoletti and MJ Buchmeier
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.
Copyright © 1997, American Society for Microbiology
Antibody prevents the establishment of persistent arenavirus infection in synergy with endogenous T cells
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
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