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
Pwhi. Parren et al., 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, AIDS, 9(6), 1995, pp. 1-6
Objective: Mice with severe combined immunodeficiency (SCID) transplan
ted with human peripheral blood lymphocytes (hu-PBL) have been shown t
o be useful as an animal model for HIV-1 infection. This model was use
d to assess the ability of a human anti-gp120 antibody to protect agai
nst HIV-1 infection. Design and methods: hU-PBL-SCID mice were injecte
d with an HIV-1 broadly neutralizing human monoclonal antibody against
the gp120 CD4-binding site prior to challenge with HIV-1(SF2). The an
tibody b12, employed for these studies, was isolated from an antibody
phage-display library prepared from bone-marrow of a long-term asympto
matic HIV-1-seropositive donor. Both Fab fragments and whole immunoglo
bulin (Ig) G1 b12 antibody were assessed for protection. Results: Fab
b12, tested at a dose approximate to 1.9mg/kg, was able to protect 25%
of hu-PBL-SCID mice from HIV-1 infection. IgG1 b12, which displayed f
avorable pharmacokinetic properties, showed a dose-dependent protectio
n that was complete with a regimen of two injections of 100 mu g per m
ouse. The in vivo protective dose of antibody at the time of virus cha
llenge was estimated to be 4.5-7 mg/kg from antibody clearance data. C
onclusions: This study demonstrates for the first time that complete p
rotection against HIV-1 infection can be achieved in the hU-PBL-SCID m
odel by passive immunization with physiologically relevant doses of a
human gp120 CD4-binding site antibody derived from natural infection.