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Non-neutralizing IgG anti-PID antibodies decreased viral load following high dose vaginal challenge of non-human primates

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HAL Id: inserm-00731779

https://www.hal.inserm.fr/inserm-00731779

Submitted on 13 Sep 2012

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Non-neutralizing IgG anti-PID antibodies decreased

viral load following high dose vaginal challenge of

non-human primates

Christiane Moog, Nathalie Dereuddre-Bosquet, Marina Elizabeth Biedma,

Sylvie Schmidt, Thomas Decoville, Isabelle Mangeot, Suzan Zolla-Pazner,

Brigitta Vcelar, Dietmar Katinger, Vincent Holl, et al.

To cite this version:

Christiane Moog, Nathalie Dereuddre-Bosquet, Marina Elizabeth Biedma, Sylvie Schmidt, Thomas

Decoville, et al.. Non-neutralizing IgG anti-PID antibodies decreased viral load following high dose

vaginal challenge of non-human primates. Retrovirology, BioMed Central, 2012, 9 (Suppl 2), pp.O38.

�inserm-00731779�

(2)

O R A L P R E S E N T A T I O N

Open Access

Non-neutralizing IgG anti-PID antibodies

decreased viral load following high dose

vaginal challenge of non-human primates

C Moog

1*

, N Dereuddre-Bosquet

2

, M Biedma

1

, S Schmidt

1

, T Decoville

1

, I Mangeot

2

, S Zolla-Pazner

3

, B Vcelar

4

,

D Katinger

4

, V Holl

5

, R Le Grand

2

From

AIDS Vaccine 2012

Boston, MA, USA. 9-12 September 2012

Background

Fc-mediated inhibitory activity of neutralizing antibodies has been shown to participate in HIV protection (Hessell et al. 2007). In addition, a non-neutralizing antibody F240 was found to partially protect macaques from SHIV vaginal transmission (Moore et al., 2011). However, mechanisms involved in this protection need further investigations. In this study, two non-neutralizing antibo-dies have been selected on the basis of their Fc-mediated inhibitory functions in vitro for further analysis of their protective role on vaginal challenge in non-human primate (NHP).

Methods

We have assessed and scored various in vitro HIV-inhibitory activities of non-neutralizing antibodies: Fc-mediated inhibition of macrophages through phago-cytosis of immunecomplexes, ADCC in primary infected CD4+ T lymphocytes by autologous NK cells, capture of native primary virus particles. Efficacy of two anti-PID antibodies with high in vitro functional scores has been tested in NHP. The combination of two antibodies for-mulated in 1.6% HEC gel has been topically applied in the vagina of macaques (n=6), 1 hour before vaginal challenge with high dose (10 AID50) of SHIVSF162P3. Infection was followed by assessing viral load in the plasma.

Results

Although unable to block virus entry at mucosal site as all treated animals became persistently infected, the

antibody treated macaques have significant decrease of plasma viral load (day 7, p=0.0479; day 14, p=0.0351, day 42: p=0.0370).

Conclusion

Decrease in viral load following antibody treatment strongly suggests that non-neutralizing inhibitory anti-bodies could interfere with early viral replication and dissemination through Fc-mediated inhibitory functions. Additional studies will be required to optimize this inhi-bition, and combined strategies should be developed to assess the potential synergy between neutralizing and non-neutralizing inhibitory antibodies.

Author details

1

INSERM, Strasbourg, France.2CEA, Fontenay-aux-Roses, France.3NYU, New York, NY, USA.4Polymun Scientific GmbH, Vienna, Austria.5Covance,

Geneva, Switzerland.

Published: 13 September 2012

doi:10.1186/1742-4690-9-S2-O38

Cite this article as:Moog et al.: Non-neutralizing IgG anti-PID antibodies decreased viral load following high dose vaginal challenge of non-human primates. Retrovirology 2012 9(Suppl 2):O38.

1INSERM, Strasbourg, France

Full list of author information is available at the end of the article Moog et al. Retrovirology 2012, 9(Suppl 2):O38

http://www.retrovirology.com/content/9/S2/O38

© 2012 Moog et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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