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

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 a-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 a-helical state of the 4E10 epitope while maintaining a structurally less-constrained 2F5 epitope. Sprague-Dawley rats were immunized with MPERSAPNs, 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.

Induction of Antibodies Specific for Gp41 of HIV-1 by Gene Gun DNA Vaccination

“…On the other hand, immunising with VLP expressing the MPER Kandem Toukam et al [40] were able to induce MPER-specific antibodies binding the 2F5 epitope, but not neutralising. A conformation-specific display of 4E10 and 2F5 epitopes on self-assembling protein nanoparticles also failed to induce neutralising antibodies [41].…”

A silk purse from a sow's ear—bioinspired materials based on α-helical coiled coils

“…synthetic virus-like particle; SVLP) and derivations such as lipoprotein virus-like particles [49] and coiled coil based vesicles with membrane fusion properties [50 ]. Using such technologies, vaccines to malaria [51,52], toxoplasma [53] and HIV [54] are being developed, but the technology is also a useful scientific tool to target specific epitopes in any protein of interest for example [55]. It is also clear though that such virus-like structures can be used to target specific cells [56 ] and also deliver cargo, as evidenced by the proof principle experiment of encapsulating gold particles within these structures [57] to expand their biomedical application [58].…”

Tolerogenic Nanoparticles to Treat Islet Autoimmunity

“…Furthermore, the shape/structure of a nanoparticle can also be important for interaction with the immune system, especially in terms of proper conformational display of an antigen in vaccine particles [90–94]. …”