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. 1995 Jun;9(6):F1-6. doi: 10.1097/00002030-199506000-00001.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acquired Immunodeficiency Syndrome / immunology
  • Acquired Immunodeficiency Syndrome / prevention & control*
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Binding, Competitive
  • CD4 Antigens / immunology*
  • Dose-Response Relationship, Immunologic
  • HIV Envelope Protein gp120 / immunology*
  • HIV-1 / immunology*
  • Humans
  • Immunization, Passive*
  • Immunoglobulin Fab Fragments / immunology
  • Immunoglobulin G / immunology
  • Mice
  • Mice, SCID
  • Neutralization Tests


  • Antibodies, Monoclonal
  • CD4 Antigens
  • HIV Envelope Protein gp120
  • Immunoglobulin Fab Fragments
  • Immunoglobulin G