Adjuvanted multivalent vaccine targeting clinically relevant Pf bacteriophage creates cross-reactive antibodies

Abstract

Abstract Pseudomonas aeruginosa (Pa) is a bacterial pathogen associated with chronic diabetic wounds as well as potentially deadly lung infections in cystic fibrosis patients. Pa is listed by the WHO as “Priority 1” in the Priority Pathogens list and results in hundreds of deaths each year. Pa diversity presents a challenge in developing a vaccine or therapeutic capable of resolving infections caused by different Pa clinical isolates. Filamentous Pf phages (a virus) infect the majority of Pa strains. Additionally, the presence Pf phage is a key virulence factor contributing to Pa infections. Pf is a filamentous-lysogenic phage that is primarily comprised of repeats of coat protein (CoaB). A consensus peptide derived from the coat protein was identified and used as the antigen for our phage vaccine targeted vaccine. This conjugate vaccine targeting Pf phage induced protection against Pa wound challenges in mice. Additionally, our team has implemented the use of a novel TLR4 agonist to further enhance antibody response against Pf coat protein intact Pf phage virions. Based on their amino acid sequence homology, clinical isolates of Pa and associated Pf phage were divided into two major clades. We prepared CRM-197 conjugates using the consensus peptides from both clades. Vaccination with these multivalent conjugates in combination with a novel synthetic TLR4 agonist (adjuvant) boosts antibody response against the peptides and promotes antibody cross-recognition between peptides. Creating a safe and effective vaccine that can mount a robust immune response against both clades of Pf phage is an important advancement towards the development and clinical testing of phage based vaccine targeting deadly Pa infections. Supported by R01 AI138981-01