4.4 Article

Virus like particle based strategy to elicit HIV-protective antibodies to the alpha-helic regions of gp41

Journal

VIROLOGY
Volume 431, Issue 1-2, Pages 1-11

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2012.05.005

Keywords

HIV; VLP; Neutralizing antibodies; gp41; ADCC

Categories

Funding

  1. European Commission/Seventh Framework Program [201433]
  2. Bill and Melinda Gates Foundation [53030, PP1008144]

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Natural antibodies to gp41 inhibit HIV-1 replication through the recognition of two different regions, corresponding to the leucine zipper motif in the HR1 alpha-helix and to another motif within HR2 region, hosting 2F5 and 4E10 epitope. This study aimed at reproducing such protective responses through VLP vaccination. Six regions covering the alpha-helical regions of gp41 were conjugated to the surface of AP205 phage-based VLPs. Once administered in mice via systemic or mucosal route, these immunogens elicited high titers of gp41-specific IgG. Immunogenicity and HIV infectivity reduction were obtained either with HR2 regions or with peptides where aminoacid strings were added to either the C-terminus or N-terminus of core epitope in HR1 region. Antibody-dependent cell cytotoxicity (ADCC) activity was induced by one of the HR2 epitopes only. These results may have relevant implications for the development of new vaccinal approaches against HIV infection. (C) 2012 Elsevier Inc. All rights reserved.

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