Advancing technology platforms for the development of bacterial vaccines

Technology platforms represent an important innovation in development and implementation of vaccines to combat high-burden diseases and to address the increasing number and global distribution of pathogens resistant to antimicrobial drugs. Generalized Modules for Membrane Antigens (GMMA), and nanoparticles (NP) are attractive technologies for the development of effective vaccine, especially thanks to the enhancement of the antigen immunogenicity, but also for the improvement in quality and variety of subclasses of antibodies elicited. GMMA are Outer Membrane Vesicles (OMVs) naturally released from Gram-negative bacteria engineered to produce large quantities of detoxified OMVs in a detergent free process. GMMAs can be engineered for the display of homologous and heterologous selected target antigens through genetic engineering of the GMMA strain for overexpression on the GMMA surface. Protein nanoparticles (NPs) have the intrinsic ability to self-assemble into highly ordered symmetric and stable structures and can be used for displaying antigens in multicopy ordered patterns on their surface. Using as model antigen, PcrV from Pseudomonas aeruginosa, Hla from Staphylococcus aureus, and Streptococcus agalactie B pilus protein, D3, we aim to compare on non-pathogenic E. coli GMMA and NPs scaffolds platforms in terms of technical feasibility, multivalency (display of two or more antigens on the same particle) and antigen-immunogenicity enhancement. Computational and structure-based design have been applied for antigen generation. A first in vivo study focused on PcrV showed that a significantly higher antibodies titre is obtained after immunization with Ferritin and GMMA displaying the antigen, compared to mI3 display or single protein. Qualitative analysis of the anti-sera obtained further elucidate the impact of these scaffold on antigen-specific immune response.