Exploiting surface-exposed proteins to develop new therapeutic strategies against Bcc and Pseudomonas aeruginosa infections

Respiratory infections caused by Burkholderia cepacia complex (Bcc) and Pseudomonas aeruginosa remain life-threatening to Cystic Fibrosis (CF) patients. Immunotherapies are attractive alternatives to protect CF patients against these infections. In order to identify new targets for the development of immunoprotective therapies, we used a surfomics approach to find putative surface-exposed proteins. This methodology combined with immunoinformatics tools allowed the identification of surface-exposed proteins containing B-cell epitopes [1]. The OmpA-like protein BCAL2645 was chosen and demonstrated by Western blotting and ELISA assays to be immunoreactive against sera from CF patients with a record of Bcc infections. The protein was characterized as multifunctional and important in the infection process. An anti-BCAL2645 polyclonal antibody was produced and was found to decrease the number of adhered and invading B.cenocepacia bacteria to human cells in vitro by more than 70% [2]. A cross-effect against P.aeruginosa and B.multivorans using this antibody was also observed, strongly decreasing the adhesion and invasion of these species to the human bronchial epithelial cell line CFBE41o-[3]. Using the animal model Galleria mellonella, the antibody was found to confer protection against these infections. These results highlight the potential of anti-BCAL2645 antibodies for passive immunization therapies to prevent infections against two of the most problematic bacterial species infecting CF patients. Preliminary results from passive immunization strategies under study using anti-BCAL2645 antibodies will be presented.

[1] Seixas, AMM; etal. Surface-Exposed Protein Moieties of Burkholderia cenocepacia J2315 in Microaerophilic and Aerobic Conditions. Vaccines 2024,12,398. https://doi.org/10.3390/vaccines12040398

[2] Seixas, AMM; etal.. A Polyclonal Antibody Raised against the Burkholderia cenocepacia OmpA-like Protein BCAL2645 Impairs the Bacterium Adhesion and Invasion of Human Epithelial Cells In Vitro. Biomedicines 2021,9,1788. https://doi.org/10.3390/biomedicines9121788

[3] Seixas, AMM; etal. A Polyclonal Antibody against a Burkholderia cenocepacia OmpA-like Protein Strongly Impairs Pseudomonas aeruginosa and B.multivorans Virulence. Vaccines 2024,12,207. https://doi.org/10.3390/vaccines12020207