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A Strategy for Selectively Shielding Portions of a Peptide/Protein from Immune Response while Maintaining Immunogenicity of Contiguous Epitopes

  • Elisabetta Bianchi
  • Marco Finotto
  • Paolo Ingallinella
  • Mike Citron
  • Renee Hrin
  • Meiqing Lu
  • Romas Geleziunas
  • Michael D. Miller
  • Xiaoping Liang
  • Antonello Pessi
Part of the Advances in Experimental Medicine and Biology book series (volume 611)

Introduction

Considerable effort is being dedicated to devise vaccination strategies to elicit a humoral response against human immunodeficiency virus (HIV). Recently we validated the fusogenic gp41 subunit of the envelope glycoprotein as a vaccine target by discovering a neutralizing antibody, D5 that inhibits HIV entry by preventing formation of the 6-helix bundle [1]. IgG D5 binds to a highly conserved hydrophobic pocket in the groove formed by the trimeric coiled coil of the gp41 N-helices.

We designed peptides that are mimetics of the gp41 trimeric N-helix coiled coil. These chimeric peptides, such as (CCIZN17)3, comprise a designed coiled coil scaffold with a covalent stabilizing moiety and a region of the HIV N-helix sequence [2]. Our aim is to use peptide vaccines of this class to raise D5-like antibodies that target the HIV N portion. However, when using our chimeric peptides, a substantial amount of antibodies are directed against the scaffold IZ. To circumvent this, we have...

Keywords

Human Immunodeficiency Virus Vaccination Strategy Coiled Coil Conformational Epitope Boost Injection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Miller, M.D. et al. Proc. Natl. Acad. Sci. USA 102, 14759 (2005).CrossRefGoogle Scholar
  2. 2.
    Bianchi, E. et al. Proc. Natl. Acad. Sci. USA 102, 1290 (2005).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Elisabetta Bianchi
    • 1
  • Marco Finotto
    • 1
  • Paolo Ingallinella
    • 1
  • Mike Citron
    • 2
  • Renee Hrin
    • 2
  • Meiqing Lu
    • 2
  • Romas Geleziunas
    • 2
  • Michael D. Miller
    • 2
  • Xiaoping Liang
    • 2
  • Antonello Pessi
    • 1
  1. 1.IRBM-MRL Peptide Centre of ExcellencePomeziaItaly
  2. 2.Merck Research LaboratoriesWest PointUSA

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