Immunomodulatory Nanoparticles from Elastin-Like Recombinamers: Single-Molecules for Tuberculosis Vaccine Development

Abstract

This study investigates both the physicochemical properties and immunogenicity of a genetically engineered elastin-like block corecombinamer (ELbcR) containing a major membrane protein sequence from Mycobacterium tuberculosis. The recombinant production of this ELbcR allows the production of large quantities of safe, antigenic particle-based constructs that directly and reversibly self-assemble into highly biocompatible, multivalent, monodisperse, and stable nanovesicles with a diameter of 55 nm from the same gene product using a highly efficient and cost-effective inverse transition cycling (ITC) procedure. The compositional complexity of these vesicles is retained after secondary processes such as endotoxin removal, sterilization, and lyophilization. An initial pro-chemotactic cytokine response (IL-1β) followed by a pro-Th2/IL-5 response was observed in mice plasma following subcutaneous administration of the antigen-loaded nanovesicles in mice. This biphasic model of cytokine production was coupled with humoral isotype switching from IgM- to IgG-specific antibodies against the antigen, which was only observed in the presence of both the antigen and the polymer in the same construct and in the absence of additional adjuvants.

Immune-tolerant elastin-like polypeptides (iTEPs) and their application as CTL vaccine carriers

“…In summary, an ability to precisely control the immunogenicity and functionality of ELPs is important to using the materials in delivering immunotherapeutics, which is still at its infancy. (68) …”

Elastin-like polypeptides: Therapeutic applications for an emerging class of nanomedicines

“…The preferential IgG binding to rSj67 (4.7-fold greater median fluorescence) in the sera of 13 schistosomiasis japonica infected volunteers relative to five uninfected controls was confirmed using bead-based ELISA. Additional diseases for which potential ELP-based vaccines are being explored include tuberculosis [157, 158], influenza[159, 160], and Psittacine beak and feather disease[161]. …”

Recent Contributions of Elastin-Like Recombinamers to Biomedicine and Nanotechnology

“…One of the most recent publications in this sense describes the production of a vaccine carrier in which an amphiphilic ELR is co-expressed with an antigenic peptide from a major membrane protein present in M. tuberculosis (Fig. 3) [124]. Above the Tt, the fusion construct self-assembles into a nanovesicle of 60 nm (similar to the size of many pathogens) in which the antigenic motif is displayed at the surface.…”

“…Self-assembly of the ELR into spherical nanoparticles displaying a corona of antigens from a M. tuberculosis major membrane protein. Cryo-TEM image shows the morphological property of the assembly [124]. Adapted with permission from reference [115].…”