Engineered Curli Nanofilaments as a Self‐Adjuvanted Antigen Delivery Platform

• Published in: Advanced healthcare materials 2023-08, Vol.12 (21), p.e2300224-n/a
• Main Authors: Lamontagne, Félix, Arpin, Dominic, Côté‐Cyr, Mélanie, Khatri, Vinay, St‐Louis, Philippe, Gauthier, Laurie, Archambault, Denis, Bourgault, Steve
• Format: Article
• Language: English
• Subjects: Adjuvants; Adjuvants, Immunologic; Animals; Antibodies, Viral; antigen delivery platforms; Antigen-presenting cells; Antigens; Autoantigens; Biofilms; curli‐specific gene A; Dendritic cells; Experimental infection; Humans; Immune response (cell-mediated); Immune response (humoral); Immune system; immunostimulants; Immunostimulation; Infectious diseases; Influenza; Influenza A; influenza A virus; Influenza A Virus, H1N1 Subtype; Influenza Vaccines; Influenza, Human; Inoculation; Mice; Mice, Inbred BALB C; nanofilaments; Nanoparticles; nanovaccines; Proteins; Robustness; Viral Matrix Proteins; Viruses
• ISSN: 2192-2640; 2192-2659; 2192-2659
• DOI: 10.1002/adhm.202300224

Proteinaceous nanoparticles constitute efficient antigen delivery systems in vaccine formulations due to their size and repetitive nature that mimic most invading pathogens and promote immune activation. Nonetheless, the coadministration of an adjuvant with subunit nanovaccines is usually required to induce a robust, long‐lasting, and protective immune response. Herein, the protein Curli‐specific gene A (CsgA), which is known to self‐assemble into nanofilaments contributing to bacterial biofilm, is exploited to engineer an intrinsically immunostimulatory antigen delivery platform. Three repeats of the M2e antigenic sequence from the influenza A virus matrix 2 protein are merged to the N‐terminal domain of engineered CsgA proteins. These chimeric 3M2e‐CsgA spontaneously self‐assemble into antigen‐displaying cross‐β‐sheet nanofilaments that activate the heterodimeric toll‐like receptors 2 and 1. The resulting nanofilaments are avidly internalized by antigen‐presenting cells and stimulate the maturation of dendritic cells. Without the need of any additional adjuvants, both assemblies show robust humoral and cellular immune responses, which translate into complete protection against a lethal experimental infection with the H1N1 influenza virus. Notably, these CsgA‐based nanovaccines induce neither overt systemic inflammation, nor reactogenicity, upon mice inoculation. These results highlight the potential of engineered CsgA nanostructures as self‐adjuvanted, safe, and versatile antigen delivery systems to fight infectious diseases. The protein Curli‐specific gene A, which is known to self‐assemble into nanofilaments contributing to bacterial biofilm, is engineered to design an intrinsically immunostimulatory antigen delivery nanoplatform for vaccination purpose. These assemblies harboring a conserved influenza A antigen show robust humoral and cellular immune responses, which translate into complete protection against a lethal experimental infection with the H1N1 influenza virus.