title: Potent human immunodeficiency virus-neutralizing and complement lysis activities of antibodies are not obligatorily linked.
abstract: To evaluate the contribution of complement-mediated lysis to the in vivo activities of neutralizing antibodies, we analyzed the influence of complement activation on treatment success in a recent passive immunization trial with the neutralizing monoclonal antibodies 2G12, 2F5, and 4E10. Administration of monoclonal antibodies led to an immediate, high activation of the complement system even in the absence of viremia in the 14 participating human immunodeficiency virus-infected individuals. Lysis activity measured in patient plasma increased during passive immunization; however, the increases were modest and only partially attributable to the administration of antibodies. We found that unlike neutralization activity, lysis activity was not associated with treatment success in this trial. Compared to complement lysis mounted by the polyclonal antibody response in vivo, monoclonal antibodies were weak inducers of this activity, suggesting that polyclonal responses are more effective in reaching the required threshold of complement activation. Importantly, strong neutralization activity of the monoclonal antibodies did not predict complement lysis activity against patient and reference viruses, suggesting that these activities are not linked. In summary, our data support the notion that the in vivo activities of 2G12, 2F5, and 4E10 are likely due to direct neutralization or Fc receptor-mediated mechanisms such as phagocytosis and antibody-dependent cellular cytotoxicity.
authors.affiliation: Division of Infectious Diseases, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland. alexandra.trkola@usz.ch
authors.forename: Michael
authors.initials: M
authors.lastname: Huber
authors.forename: Viktor
authors.initials: V
authors.lastname: von Wyl
authors.forename: Christoph G
authors.initials: CG
authors.lastname: Ammann
authors.forename: Herbert
authors.initials: H
authors.lastname: Kuster
authors.forename: Gabriela
authors.initials: G
authors.lastname: Stiegler
authors.forename: Hermann
authors.initials: H
authors.lastname: Katinger
authors.forename: Rainer
authors.initials: R
authors.lastname: Weber
authors.forename: Marek
authors.initials: M
authors.lastname: Fischer
authors.forename: Heribert
authors.initials: H
authors.lastname: Stoiber
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Alexandra
authors.initials: A
authors.lastname: Trkola
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D003167:Complement Activation / Q000276:immunology; D003176:Complement C3 / Q000032:analysis; D015938:Complement Membrane Attack Complex / Q000032:analysis; D003165:Complement System Proteins / Q000276:immunology*; D006678:HIV / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D007116:Immunization, Passive; D009500:Neutralization Tests; D010949:Plasma / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D003176:Complement C3; D015938:Complement Membrane Attack Complex; D015483:HIV Antibodies; D003165:Complement System Proteins