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This article is part of the supplement: Frontiers of Retrovirology 2011

Open Access Poster presentation

Stable HIV-1 envelope glycoprotein immune complexes as vaccine immunogens

Thijs van Montfort1*, Mark Melchers1, Tony MM van Capel2, Ester C de Jong2, William A Paxton1 and Rogier W Sanders1

  • * Corresponding author: Thijs van Montfort

Author Affiliations

1 Laboratory of Experimental Virology, Department of Medical Microbiology, Academic Medical Center of the University of Amsterdam, Amsterdam 1105AZ, The Netherlands

2 Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam 1105AZ, The Netherlands

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Retrovirology 2011, 8(Suppl 2):P75  doi:10.1186/1742-4690-8-S2-P75


The electronic version of this article is the complete one and can be found online at: http://www.retrovirology.com/content/8/S2/P75


Published:3 October 2011

© 2011 van Montfort 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.

Poster presentation

The development of an HIV-1 vaccine that elicits strong neutralizing antibody (nAb) and T cell responses is challenging. Classical vaccine strategies such as live attenuated vaccines are considered unsafe whereas envelope glycoprotein (Env)subunit vaccines induce low nAb titers that do not protect against HIV-1 infection. We showed previously that most HIV-1-antibody immune complexes (HIV-ICs) formed with either broadly nAbs or Abs derived from patient sera dissociate into free HIV-1 virions and Ab when captured by dendritic cells (DCs). Dissociation of HIV-ICs allows for transmission from DCs to CD4+ T target cells. H but more importantly it can hamper the activation of immune cells which is a hallmark of stable ICs. The natural role of ICs is enhancing uptake by DCs, DC activation, induction of antigen presentation and induction of T cell responses. Furthermore, ICs are captured by follicular DCs that activate the B cells for Ab production, Ab affinity maturation and ísotype switching. We explore stable Env-ICs as a vaccine candidate. To form stable Env-ICs we fused the Fc-region of immunoglobulins to trimeric gp140. Env-IC maintained a native Env conformation which was evaluated by ELISA with Env-specific Abs. Native PAGE analyses and size exclusion chromatography showed that Env-ICs formed trimers, but hexamers consisting of 2 Env trimers and 3 dimeric Fc-tails were also observed. The functionality of the Fc-tail was evaluated by immuno-precipitation of the Env-IC with protein-G couple beads. Capture of Env-IC by DCs was enhanced with 50% compared to wild-type Env. Moreover, Env-IC captured by DCs more efficiently activated gp120-specificT helper cells.

Acknowledgements

This research was supported by the Dutch AIDS fund, grants #2008013 and #2009012.