Conformation-specific Display of 4E10 and 2F5 Epitopes on Self-assembling Protein Nanoparticles as a Potential HIV Vaccine

Authors

  • Newton Wahome,

    1. Molecular and Cell Biology Department and Institute of Materials Science, University of Connecticut, 97 N. Eagleville Road, Storrs, CT 06250, USA
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  • Tanya Pfeiffer,

    1. Forschungsschwerpunkt Infektion und Krebs, F020, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany
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  • Ina Ambiel,

    1. Department für Infektiologie, Virologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
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  • Yongkun Yang,

    1. Molecular and Cell Biology Department and Institute of Materials Science, University of Connecticut, 97 N. Eagleville Road, Storrs, CT 06250, USA
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  • Oliver T. Keppler,

    1. Department für Infektiologie, Virologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
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  • Valerie Bosch,

    1. Forschungsschwerpunkt Infektion und Krebs, F020, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany
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  • Peter Burkhard

    Corresponding author
    1. Molecular and Cell Biology Department and Institute of Materials Science, University of Connecticut, 97 N. Eagleville Road, Storrs, CT 06250, USA
      Corresponding authors: Peter Burkhard, peter.burkhard@uconn.edu; Valerie Bosch, v.bosch@dkfz-heidelberg.de
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Corresponding authors: Peter Burkhard, peter.burkhard@uconn.edu; Valerie Bosch, v.bosch@dkfz-heidelberg.de

Abstract

The self-assembling protein nanoparticle (SAPN) is an antigen-presenting system that has been shown to be suitable for use as a vaccine platform. The SAPN scaffold is based on the principles of icosahedral symmetry, beginning from a monomeric chain that self-assembles into an ordered oligomeric state. The monomeric chain contains two covalently linked α-helical coiled-coil domains, an N-terminal de novo-designed pentameric tryptophan zipper and a C-terminal de novo-designed trimeric leucine zipper, which assemble along the internal symmetry axes of an icosahedron. In this study, we incorporated the membrane proximal external region (MPER) of HIV-1 gp41 from HXB2 into the N-terminal pentamer, referred to as MPER-SAPN, attempting to reproduce the α-helical state of the 4E10 epitope while maintaining a structurally less-constrained 2F5 epitope. Sprague–Dawley rats were immunized with MPER-SAPNs, and their sera were analyzed for induced humoral anti-HIV-1 responses. We show that high membrane proximal external region-specific titers can be raised via the repetitive antigen display of MPER on the SAPN without the need for adjuvant. However, none of the sera displayed a detectable neutralizing activity against HIV-1. Thus, 4E10- and 2F5-like neutralizing antibodies could not be elicited by MPER conformationally restrained in the SAPN context.

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