Involvement of the complement system in antibody-mediated post-exposure protection against human immunodeficiency virus type 1.
We previously reported that passive transfer of a murine V3-specific monoclonal antibody (BAT123) to hu-PBL-SCID mice challenged with HIV-1LAI confers postexposure protection from infection. The role of the Fc fragment of this antibody as well as the involvement of the complement system in protection were evaluated in vivo. When we compared the postexposure protection offered by BAT123 and CGP 47439, a chimeric form of BAT123 in which the murine Fc domain has been replaced by a human IgG1 Fc domain, CGP 47439 failed to provide postexposure protection against HIV-1LAI despite having similar pharmacokinetics and in vitro neutralizing activity. Furthermore, when hu-PBL-SCID mice were treated with cobra venom factor, which inactivates serum complement activity, the postexposure protective ability of BAT123 was abrogated. These findings suggest that the complement system is involved in the passive protection against HIV-1 infection conferred by the murine monoclonal antibody BAT123 in hu-PBL-SCID mice.
Gauduin
M C
MC
The Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016, USA.
Weir
R
R
Fung
M S
MS
Koup
R A
RA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology; D015941:Complement Hemolytic Activity Assay; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D003165:Complement System Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000494:pharmacology; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013154:Spleen / Q000821:virology
D000911:Antibodies, Monoclonal; D003169:Complement Inactivator Proteins; D004546:Elapid Venoms; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007141:Immunoglobulin Fc Fragments; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C016310:cobra venom factor; D003165:Complement System Proteins