Conformation-specific display of 4E10 and 2F5 epitopes on self-assembling protein nanoparticles as a potential HIV vaccine

• Verfasst von: Wahome, Newton [VerfasserIn]
• Verfasst von: Ambiel, Ina [VerfasserIn]
• Verfasst von: Keppler, Oliver Till [VerfasserIn]
• Titel: Conformation-specific display of 4E10 and 2F5 epitopes on self-assembling protein nanoparticles as a potential HIV vaccine
• Verf.angabe: Newton Wahome, Tanya Pfeiffer, Ina Ambiel, Yongkun Yang, Oliver T. Keppler, Valerie Bosch and Peter Burkhard
• Umfang: 9 S.
• Fussnoten: First published: 31 May 2012 ; Gesehen am 27.06.2018
• Titel Quelle: Enthalten in: Chemical biology and drug design
• Jahr Quelle: 2012
• Band/Heft Quelle: 80(2012), 3, S. 349-357
• ISSN Quelle: 1747-0285
• DOI: doi:10.1111/j.1747-0285.2012.01423.x
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1576894541

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.