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Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies

Abstract

To determine the protective potential of the humoral immune response against HIV-1 in vivo we evaluated the potency of three neutralizing antibodies (2G12, 2F5 and 4E10) in suppressing viral rebound in six acutely and eight chronically HIV-1–infected individuals undergoing interruption of antiretroviral treatment (ART). Only two of eight chronically infected individuals showed evidence of a delay in viral rebound during the passive immunization. Rebound in antibody-treated acutely infected individuals upon cessation of ART was substantially later than in a control group of 12 individuals with acute infection. Escape mutant analysis showed that the activity of 2G12 was crucial for the in vivo effect of the neutralizing antibody cocktail. By providing further direct evidence of the potency, breadth and titers of neutralizing antibodies that are required for in vivo activity, these data underline both the potential and the limits of humoral immunity in controlling HIV-1 infection.

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Figure 1: Analysis of viral rebound upon cessation of ART in 14 passively immunized subjects.
Figure 2: Comparison of virus rebound in acutely infected subjects with and without passive immunization.
Figure 3: Antibody escape.
Figure 4: Response analysis.

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Acknowledgements

Support was provided by the Swiss National Science Foundation (grant PP00B-102647 to A.T. and grant 3100A0-103748 to H.G. and A.T.), research grants from the Union Bank of Switzerland, the Gebert-Rüf foundation (P-041/02) and the FAIR Foundation to A.T. and H.G., and by a research grant of the Kanton Zürich. We thank our patients for their commitment, M. Winniger, U. Berberat, R. Hafner, B. Hasse, U. Karrer, R. Oberholzer, C. Schneider and C. Grube for patient care, J. Böni and F. Burgener for technical help, M. Schlumpf for infrastructural help, E. Gremlich for study monitoring, I. Nievergelt for administrative assistance and H. Hengartner and R. Zinkernagel for their support in initiating this study.

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Correspondence to Alexandra Trkola or Huldrych F Günthard.

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Competing interests

Gabriela Stiegler, Brigitta Vcelar and Hermann Katinger are from Polymun Scientific, a company whose aim is to advance the development of the human monoclonal antibodies from clinical trials to market approval for prevention and treatment of HIV infection.

Supplementary information

Supplementary Fig. 1

Viremia rebounds during previous STIs in chronic patients participating in passive immunization trial. (PDF 81 kb)

Supplementary Fig. 2

Characteristics of patients with acute HIV-1 infection. (PDF 97 kb)

Supplementary Table 1

Patient characteristics (PDF 24 kb)

Supplementary Table 2

Pharmacokinetic parameters (PDF 18 kb)

Supplementary Table 3

History of treatment interruption of chronically infected individuals participating in passive immunization trial (PDF 25 kb)

Supplementary Table 4

Sequence analysis of 2F5 and 4E10 epitope (PDF 14 kb)

Supplementary Table 5

Antibody sensitivity of sequential isolates derived during STIs (PDF 16 kb)

Supplementary Note (PDF 38 kb)

Supplementary Methods (PDF 25 kb)

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Trkola, A., Kuster, H., Rusert, P. et al. Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies. Nat Med 11, 615–622 (2005). https://doi.org/10.1038/nm1244

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