Pseudomonas aeruginosa elongation factor-Tu (EF-Tu) is an immunogenic protective protein antigen

• Published in: Vaccine 2024-12, Vol.42 (26), p.126476, Article 126476
• Main Authors: Moustafa, Dina A., Lou, Emma, Schafer-Kestenman, Morgan E., Mateu-Borrás, Margalida, Doménech-Sanchez, Antonio, Albertí, Sebastián, Goldberg, Joanna B.
• Format: Article
• Language: English
• Subjects: Acute pneumonia; Adult; Animals; Antibiotic resistance; Antibodies; Antibodies, Bacterial - blood; Antibodies, Bacterial - immunology; Antigens; Antigens, Bacterial - immunology; Antisera; Bacteremia; Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Bronchopulmonary infection; COVID-19; Cystic fibrosis; E coli; Elongation; Elongation factor-Tu; Female; Glycerol; Hospitals; Humans; Immune response; Immune system; Immunization; Immunogenicity; Male; Mice; Middle Aged; Nosocomial infection; Opportunist infection; Passive immunotherapy; Pathogens; Peptide Elongation Factor Tu - genetics; Peptide Elongation Factor Tu - immunology; Phosphatase; Pneumonia; Protein biosynthesis; Protein synthesis; Proteins; Pseudomonas aeruginosa; Pseudomonas aeruginosa - immunology; Pseudomonas aeruginosa - pathogenicity; Pseudomonas Infections - immunology; Pseudomonas Infections - prevention & control; Pseudomonas Vaccines - immunology; Sodium; Software; Vaccine candidate; Vaccines
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2024.126476

Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen that infects immunocompromised individuals, especially in the hospital setting. This bacterium is an important pathogen in people with weakened immune systems, injuries, and other underlying physiologic dysfunctions. P. aeruginosa is responsible for up to 20 % of all hospital-acquired pneumonias. It is one of the major causes of nosocomial infections and has been noted to be one of the most common bacteria co-infecting patients with COVID-19 or causing super-infections following COVID-19 infections. Despite improvements in antimicrobial therapy and hospital care, P. aeruginosa bacteremia and pneumonia remain fatal in about 30 % of cases. P. aeruginosa is also the leading cause of chronic life-threatening lung infections in cystic fibrosis patients. This bacterium is naturally antibiotic resistant, and infections are notoriously difficult to treat once established, with no vaccine available. We have previously shown that elongation factor-Tu (EF-Tu), a protein best known for its role in protein synthesis, is surface exposed on P. aeruginosa. As this protein is highly expressed, evolutionally conserved, and essential, we hypothesized it would make a good vaccine target. In this study, we found that P. aeruginosa EF-Tu is immunogenic in people, and that mice can develop an immune response following immunization with recombinant P. aeruginosa EF-Tu. Furthermore, immunized mice were protected from subsequent P. aeruginosa pneumonia and transfer of this vaccine antisera to naïve mice resulted in decreased colonization. Altogether these findings support the consideration of EF-Tu as a new vaccine candidate against P. aeruginosa. •P. aeruginosa elongation factor-Tu (EF-Tu) is recognized by the human immune system.•Mice immunized with recombinant P. aeruginosa EF-Tu mount a robust antibody response.•Intranasal immunization of mice with EF-Tu provides protection from acute pneumonia.•Passive transfer of sera leads to decreased colonization following intranasal infection.