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J. Virol. doi:10.1128/JVI.02569-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Potent HIV-Neutralizing and Complement Lysis Activity of Antibodies Are Not Obligatorily Linked

Division of Infectious Diseases, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland, Section of Hygiene and Medical Microbiology, Innsbruck Medical University, Fritz-Pregl-Strasse 3, 6020 Innsbruck, Austria, Polymun Scientific, Nussdorfer Lände 11, 1190 Vienna, Austria

^* To whom correspondence should be addressed. Email: alexandra.trkola{at}usz.ch.

	Abstract

To evaluate the contribution of complement-mediated lysis to the in vivo activity 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 absence of viremia in the fourteen participating HIV infected individuals. Lysis activity measured in patient plasma increased during passive immunization, however, the increases were modest and only partially attributable to administration of the 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 monoclonals 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 activity of 2G12, 2F5 and 4E10 is likely due to direct neutralization or FcR-mediated mechanisms such as phagocytosis and antibody-dependent cellular cytotoxicity.