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 approximately 1.9 mg/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 micrograms 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.
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 approximately 1.9 mg/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 micrograms 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 humangp120 CD4-binding site antibody derived from natural infection.
Authors: Donald N Forthal; Gary Landucci; Kelly Stefano Cole; Marta Marthas; Juan C Becerra; Koen Van Rompay Journal: J Virol Date: 2006-09 Impact factor: 5.103
Authors: A De Logu; R A Williamson; R Rozenshteyn; F Ramiro-Ibañez; C D Simpson; D R Burton; P P Sanna Journal: J Clin Microbiol Date: 1998-11 Impact factor: 5.948
Authors: M B Zwick; A F Labrijn; M Wang; C Spenlehauer; E O Saphire; J M Binley; J P Moore; G Stiegler; H Katinger; D R Burton; P W Parren Journal: J Virol Date: 2001-11 Impact factor: 5.103
Authors: Takayuki Ota; Colleen Doyle-Cooper; Anthony B Cooper; Michael Huber; Emilia Falkowska; Katherine J Doores; Lars Hangartner; Khoa Le; Devin Sok; Joseph Jardine; Jeffrey Lifson; Xueling Wu; John R Mascola; Pascal Poignard; James M Binley; Bimal K Chakrabarti; William R Schief; Richard T Wyatt; Dennis R Burton; David Nemazee Journal: J Immunol Date: 2012-10-12 Impact factor: 5.422
Authors: Ann J Hessell; Eva G Rakasz; Pascal Poignard; Lars Hangartner; Gary Landucci; Donald N Forthal; Wayne C Koff; David I Watkins; Dennis R Burton Journal: PLoS Pathog Date: 2009-05-15 Impact factor: 6.823