Conformation-specific display of 4E10 and 2F5 epitopes on self-assembling protein nanoparticles as a potential HIV vaccine
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 stat...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2012
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| In: |
Chemical biology and drug design
Year: 2012, Volume: 80, Issue: 3, Pages: 349-357 |
| ISSN: | 1747-0285 |
| DOI: | 10.1111/j.1747-0285.2012.01423.x |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1111/j.1747-0285.2012.01423.x Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1747-0285.2012.01423.x 
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| Author Notes: | Newton Wahome, Tanya Pfeiffer, Ina Ambiel, Yongkun Yang, Oliver T. Keppler, Valerie Bosch and Peter Burkhard |
| Summary: | 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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| Item Description: | First published: 31 May 2012 Gesehen am 27.06.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1747-0285 |
| DOI: | 10.1111/j.1747-0285.2012.01423.x |