Systemic immunization with conserved pilus-associated adhesins protects against mucosal infections

Area of Science:

• Microbiology
• Immunology
• Vaccinology

Background:

• Uropathogenic Escherichia coli (E. coli) causes most urinary tract infections (UTIs).
• Type 1 pili and their FimH adhesin are crucial for E. coli colonization of the bladder mucosa.
• Mannose receptors on bladder cells facilitate bacterial binding via FimH.

Purpose of the Study:

• To evaluate the efficacy of targeting the FimH adhesin of E. coli for UTI prevention.
• To determine if antibodies against FimH can inhibit bacterial adhesion and reduce bladder colonization.

Main Methods:

• Generating antibodies against purified FimH adhesin.
• Testing antibody inhibition of E. coli binding to bladder tissue in vitro.
• Immunizing mice systemically with FimH-containing vaccines and assessing bladder colonization in a murine cystitis model.
• Administering immune sera passively to naive mice.

Main Results:

• Antibodies against FimH inhibited E. coli binding to bladder tissue in 94% of clinical isolates.
• Systemic immunization with FimH vaccines reduced bladder colonization by over 99% in mice.
• IgG antibodies to FimH were detected in the urine of protected mice.
• Passive transfer of immune sera conferred protection against E. coli colonization.

Conclusions:

• Systemic immunization targeting the conserved FimH adhesin of uropathogenic E. coli induces effective mucosal protection.
• Anti-FimH antibodies can prevent E. coli colonization of the urogenital tract mucosa.
• This strategy holds potential for preventing recurrent and acute UTIs.