title: 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.
authors.affiliation: Bioforge Group, University of Valladolid , CIBER-BBN, Paseo de Belén 11, 47011 Valladolid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: García-Arévalo
authors.forename: Jesús F
authors.initials: JF
authors.lastname: Bermejo-Martín
authors.forename: Lucia
authors.initials: L
authors.lastname: Rico
authors.forename: Verónica
authors.initials: V
authors.lastname: Iglesias
authors.forename: Laura
authors.initials: L
authors.lastname: Martín
authors.forename: J Carlos
authors.initials: JC
authors.lastname: Rodríguez-Cabello
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Arias
mesh_terms: D004549:Elastin / Q000276:immunology*; D007155:Immunologic Factors / Q000737:chemistry / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D053758:Nanoparticles; D032581:Tuberculosis Vaccines / Q000737:chemistry / Q000276:immunology*
chemical_list: D007155:Immunologic Factors; D032581:Tuberculosis Vaccines; D004549:Elastin