Protection against HIV-1 infection in hu-PBL-SCID mice by passive immunization with a neutralizing human monoclonal antibody against the gp120 CD4-binding site.
Parren, Paul W.H.I.; Ditzel, Henrik J.; Gulizia, Richard J.; Binley, James M.; Barbas, Carlos F. III; Burton, Dennis R.; Mosier, Donald E.
9(6):1-538, June 1995.
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Objective: Mice with severe combined immunodeficiency (SCID) transplanted with human peripheral blood lymphocytes (hu-PBL) have been shown to be useful as an animal model for HIV-1 infection. This model was used to assess the ability of a human anti-gp120 antibody to protect against HIV-1 infection.
Design and methods: hu-PBL-SCID mice were injected with an HIV-1 broadly neutralizing human monoclonal antibody against the gp120 CD4-binding site prior to challenge with HIV-1SF2. The antibody b12, employed for these studies, was isolated from an antibody phage-display library prepared from bone-marrow of a long-term asymptomatic HIV-1-seropositive donor. Both Fab fragments and whole immunoglobulin (Ig) G1 b12 antibody were assessed for protection.
Results: Fab b12, tested at a dose [almost equal to]1.9mg/kg, was able to protect 25% of hu-PBL-SCID mice from HIV-1 infection. IgG1 b12, which displayed favorable pharmacokinetic properties, showed a dose-dependent protection that was complete with a regimen of two injections of 100 [mu]g per mouse. The in vivo protective dose of antibody at the time of virus challenge was estimated to be 4.5-7 mg/kg from antibody clearance data.
Conclusions: This study demonstrates for the first time that complete protection against HIV-1 infection can be achieved in the hu-PBL-SCID model by passive immunization with physiologically relevant doses of a human gp120 CD4-binding site antibody derived from natural infection.
(C) Lippincott-Raven Publishers.