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Conformation‐specific Display of 4E10 and 2F5 Epitopes on Self‐assembling Protein Nanoparticles as a Potential HIV Vaccine
Author(s) -
Wahome Newton,
Pfeiffer Tanya,
Ambiel Ina,
Yang Yongkun,
Keppler Oliver T.,
Bosch Valerie,
Burkhard Peter
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2012.01423.x
Subject(s) - epitope , gp41 , leucine zipper , pentamer , monomer , chemistry , avidity , coiled coil , context (archaeology) , heptad repeat , biophysics , antigen , virology , peptide sequence , biology , biochemistry , paleontology , organic chemistry , gene , polymer , genetics
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.