Summary
Klebsiella pneumoniae (Kp) is a significant cause of hospital-acquired infections, leading to severe diseases such as pneumonia, sepsis, and urinary tract infections. This pathogen causes large-scale outbreaks in healthcare settings, with rapid transmission and severe clinical outcomes. The prevalence of the K64 capsular type, associated with the hyper-virulent sequence type ST147, has risen dramatically from 2% of reported genomes in 2012 to over 15% in recent years, underscoring the urgency for targeted vaccine development.
This project proposes to synthesize and compare multiple glycoconjugate vaccines targeting the K64 capsular polysaccharide (CPS). By conjugating K64 CPS with selected homologous carrier proteins, we aim to induce broader protective immunity, potentially offering cross-protection against different Kp serotypes. Mice will be immunized with the different glycoconjugates, and the induced immunogenicity evaluated by analyzing sera for antigen-specific antibody responses (IgG and IgM) and functional assays such as serum bactericidal activity and opsonophagocytic killing capacity against various Kp strains.
The expected outcomes include identifying the most effective carrier protein for the K64-based glycoconjugate, developing a vaccine that provides cross-protection against multiple serotypes, and demonstrating strong immunogenicity in animal models.
This project will also pave the way for future research, such as applying the developed methodology to other capsular types and pathogens, optimizing vaccine formulations, and advancing promising candidates to clinical trials in collaboration with LMIC partners and industry. The successful development of this vaccine could significantly reduce Kp infections in both hospital and community settings, particularly benefiting LMICs where the burden of such infections is high.