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Journal of Virology, April 2008, p. 3834-3842, Vol. 82, No. 8
0022-538X/08/$08.00+0     doi:10.1128/JVI.02569-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Potent Human Immunodeficiency Virus-Neutralizing and Complement Lysis Activities of Antibodies Are Not Obligatorily Linked{triangledown} ,{dagger}

Michael Huber,1 Viktor von Wyl,1 Christoph G. Ammann,2,{ddagger} Herbert Kuster,1 Gabriela Stiegler,3 Hermann Katinger,3 Rainer Weber,1 Marek Fischer,1 Heribert Stoiber,2 Huldrych F. Günthard,1 and Alexandra Trkola1*

Division of Infectious Diseases, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland,1 Section of Hygiene and Medical Microbiology, Innsbruck Medical University, Fritz Pregl Strasse 3, 6020 Innsbruck, Austria,2 Polymun Scientific, Nussdorfer Lände 11, 1190 Vienna, Austria3

Received 3 December 2007/ Accepted 18 January 2008

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.

* Corresponding author. Mailing address: Division of Infectious Diseases, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland. Phone: 41 44 255 59 76. Fax: 41 44 255 44 99. E-mail: alexandra.trkola{at}usz.ch

{triangledown} Published ahead of print on 30 January 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{ddagger} Present address: Rocky Mountain Laboratories, NIAID, NIH, 903 South 4th Street, Hamilton, MT 59840.

Journal of Virology, April 2008, p. 3834-3842, Vol. 82, No. 8
0022-538X/08/$08.00+0     doi:10.1128/JVI.02569-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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