Immunomodulatory nanoparticles from elastin-like recombinamers: single-molecules for tuberculosis vaccine development

Area of Science:

• Biomaterials Science
• Immunology
• Molecular Biology

Background:

• Development of novel vaccine delivery systems is crucial for effective antigen presentation.
• Elastin-like recombinamers offer tunable physicochemical properties for biomaterial applications.
• Mycobacterium tuberculosis poses a significant global health challenge, necessitating improved immunotherapeutic strategies.

Purpose of the Study:

• To characterize the physicochemical properties and immunogenicity of a genetically engineered elastin-like block co-recombinamer (ELbcR).
• To evaluate the self-assembly of ELbcR into nanovesicles for antigen delivery.
• To assess the immune response elicited by ELbcR-based nanovesicles containing a Mycobacterium tuberculosis antigen.

Main Methods:

• Recombinant production of ELbcR incorporating a Mycobacterium tuberculosis membrane protein sequence.
• Inverse transition cycling (ITC) for self-assembly of nanovesicles (55 nm diameter).
• Assessment of nanovesicle stability post-endotoxin removal, sterilization, and lyophilization.
• In vivo immunogenicity studies in mice, including cytokine profiling (IL-1β, IL-5) and antibody isotype analysis (IgM, IgG).

Main Results:

• ELbcR self-assembled into stable, monodisperse nanovesicles (55 nm) with retained complexity after processing.
• Subcutaneous administration induced a biphasic cytokine response (pro-IL-1β, then pro-IL-5) in mice.
• Humoral response showed isotype switching from IgM to IgG against the antigen, dependent on antigen-polymer co-assembly.
• No additional adjuvants were required to elicit this immune response.

Conclusions:

• Genetically engineered ELbcR forms biocompatible nanovesicles suitable for vaccine development.
• The ELbcR nanovesicles effectively induce a Th2-biased immune response and antibody class switching in vivo.
• This novel biomaterial represents a promising adjuvant-free vaccine platform for targeting Mycobacterium tuberculosis and potentially other pathogens.