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
作者:
Paul Parren,
Henrik Ditzel,
Richard Gulizia,
James Binley,
Carlos Barbas,
Dennis Burton,
Donald Mosier,
期刊:
AIDS
(OVID Available online 1995)
卷期:
Volume 9,
issue 6
页码: 1-538
ISSN:0269-9370
年代: 1995
出版商: OVID
关键词: HIV-1;neutralization;passive immunization;hu-PBL-SCID mice;human anti-gp120 monoclonal antibody
数据来源: OVID
摘要:
ObjectiveMice 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 methodshu-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.ResultsFab b12, tested at a dose ≈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 μg per mouse. Thein vivoprotective dose of antibody at the time of virus challenge was estimated to be 4.5–7 mg/kg from antibody clearance data.ConclusionsThis 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.
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