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

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