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Journal of Virology, March 2005, p. 2823-2830, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.2823-2830.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Detection of Antibody-Dependent Complement-Mediated Inactivation of both Autologous and Heterologous Virus in Primary Human Immunodeficiency Virus Type 1 Infection{dagger}

Marlén M. I. Aasa-Chapman,1,{ddagger} Sophie Holuigue,1,{ddagger} Keith Aubin,1 MaiLee Wong,2 Nicola A. Jones,2 David Cornforth,3 Pierre Pellegrino,3 Philippa Newton,3 Ian Williams,3 Persephone Borrow,2 and Áine McKnight1*

Wohl Virion Centre, Windeyer Institute of Medical Sciences,1 Centre for Sexual Health and HIV Research, University College London, London,3 The Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire, United Kingdom2

Received 28 July 2004/ Accepted 15 October 2004

Specific CD8 T-cell responses to human immunodeficiency virus type 1 (HIV-1) are induced in primary infection and make an important contribution to the control of early viral replication. The importance of neutralizing antibodies in containing primary viremia is questioned because they usually arise much later. Nevertheless antienvelope antibodies develop simultaneously with, or even before, peak viremia. We determined whether such antibodies might control viremia by complement-mediated inactivation (CMI). In each of seven patients studied, antibodies capable of CMI appeared at or shortly after the peak in viremia, concomitantly with detection of virus-specific T-cell responses. The CMI was effective on both autologous and heterologous HIV-1 isolates. Activation of the classical pathway and direct viral lysis were at least partly responsible. Since immunoglobulin G (IgG)-antibodies triggered the CMI, specific memory B cells could also be induced by vaccination. Thus, consideration should be given to vaccination strategies that induce IgG antibodies capable of CMI.

* Corresponding author. Mailing address: Windeyer Institute of Medical Sciences, Wohl Virion Centre, 46 Cleveland St., London W1T 4JF, United Kingdom. Phone: 44 20 7679 9581. Fax: 44 20 7679 9555. E-mail: a.mcknight{at}ucl.ac.uk.

{dagger} Publication no. 90 from the Edward Jenner Institute for Vaccine Research.

{ddagger} M.M.I.A.-C. and S.H contributed equally to this study.

Journal of Virology, March 2005, p. 2823-2830, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.2823-2830.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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