6gut

Publication Abstract from PubMed

Non-typeable Haemophilus influenzae (NTHi) is a pathogen known for being a frequent cause of acute otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. In the present study, a vaccine antigen has been developed based on the fusion of two known NTHi adhesive proteins, Protein E (PE) and pilin subunit (PilA). The quality of the combined antigen was investigated through functional, biophysical and structural analyses. It was shown that PE and PilA individual structures are not modified in the PE-PilA fusion and that PE-PilA assembles as a dimer in solution, reflecting PE dimerization. PE-PilA was found to bind vitronectin in ELISA, as isolated PE does. Disulfide bridges were conserved and homogeneous, which was determined by peptide mapping and Top-down analysis on PE, PilA and PE-PilA molecules. Finally, the PE-PilA crystal showed a PE entity with a 3D-structure similar to that of recently published isolated PE, while the structure of the PilA entity was similar to that of a 3D-model elaborated from two other type 4 pilin subunits.Taken together, our observations suggest that the two tethered proteins behave independently within the chimeric molecule and display structures similar to the respective isolated antigens, which are important characteristics for eliciting an optimal antibody-mediated immunity. PE and PilA can thus be further developed as a single fusion protein in a vaccine perspective, in the knowledge that tethering the two antigens does not perceptibly compromise the structural attributes offered by the individual antigens.

Design and characterization of PE-PilA, a candidate fusion antigen for non-typeable Haemophilus influenzae vaccine.,Blais N, Somers D, Faubert D, Labbe S, Castado C, Ysebaert C, Gagnon LP, Champagne J, Gagne M, Martin D Infect Immun. 2019 May 13. pii: IAI.00022-19. doi: 10.1128/IAI.00022-19. PMID:31085711^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.