Advancing Vaccine Research for the Prevention of Urinary Tract Infections
Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, with extraintestinal pathogenic Escherichia coli (ExPEC) being a major causative agent. The growing prevalence of antimicrobial resistance has increased the need for alternative preventive strategies, including vaccines. In a recent publication in npj Vaccines, ZoBio collaborated with Johnson and Johnson on research investigating novel vaccine candidates for the prevention of urinary tract infections.
The study focuses on FimH, a bacterial adhesin that plays a crucial role in the early stages of infection by enabling bacteria to attach to cells in the urinary tract. A structure-guided approach was used to design a conformationally stabilized FimH lectin domain (FimHLD) antigen and explore its potential as a vaccine candidate. The antigen was evaluated in several vaccine formats, including native fimbrial tip assemblies, carrier protein-based constructs, and multivalent nanoparticles. By assessing functional antibody responses in relevant animal models, the researchers aimed to identify promising FimH-based vaccine candidates for preventing urinary tract infections (UTIs) caused by extraintestinal pathogenic Escherichia coli (ExPEC).
ZoBio contributed to both the rational design of FimH variants and their biophysical characterization. Using a combination of Surface Plasmon Resonance (SPR) and two-dimensional Nuclear Magnetic Resonance (2D-NMR), the team designed and investigated FimH mutants and demonstrated that the combined Phe71Tyr and Phe144Val mutations stabilize FimH in a tense, low-affinity conformation. This engineered variant, termed LAFimHLD, exhibited substantially reduced mannose-binding activity while maintaining structural integrity, providing important insights for the rational design of improved FimH-based vaccine candidates.
The publication showcases how combining expertise in protein engineering, immunology, and biophysical characterization can accelerate the development of novel approaches to combat infectious diseases. We are proud to have contributed to this collaborative effort and to support research aimed at advancing next-generation vaccines for the prevention of UTIs.