Development of fimbriae-based vaccine strategies for the control of urinary tract infections caused by Klebsiella pneumoniae

• Grant number: 25/06056-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2025
• End date: July 31, 2030
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Michelle Darrieux Sampaio Bertoncini
• Grantee: Vitória Giovanna Valim Pinto
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil
• Associated research grant: 23/10579-8 - EVALUATION OF TYPE I AND TYPE III FRIMBRIAE COMPONENTS AS VACCINE CANDIDATES AGAINST Klebsiella pneumoniae INFECTIONS, AP.R

Abstract

Klebsiella pneumoniae is an opportunistic pathogen responsible for high rates of hospital-acquired infections, primarily affecting children, the elderly, and immunocompromised individuals. It is also the second most common cause of urinary tract infections (UTIs). The high mortality and morbidity rates associated with K. pneumoniae infections, together with the rising prevalence of antimicrobial-resistant strains, have prompted research into strategies for preventing infections caused by this pathogen. In this context, a promising approach is the development of vaccines against K. pneumoniae. Several vaccine strategies have been investigated, including formulations based on whole bacteria or their virulence factors. Fimbriae are surface structures of Klebsiella and are considered an important virulence factor, as they enable bacterial adhesion to host surfaces and are involved in biofilm formation. Fimbrial subunits exhibit immunogenic potential, and their high prevalence and exposure on the bacterial surface make them attractive vaccine candidates for preventing infections caused by this pathogen. Based on this information, the present project aims to develop vaccine formulations based on fimbrial components for the control of UTIs caused by K. pneumoniae. Fimbrial subunits of types I (FimA) and III (MrkA), produced recombinantly in Escherichia coli, will be evaluated in combination with different adjuvants, as well as recombinant BCG expressing these proteins. Subcutaneous and local immunization routes will be compared regarding the immune response induced and protection against urinary tract infection. Cytokine production, inflammatory parameters, and bladder function will be assessed by comparing vaccinated and control groups. Antibodies generated by vaccination will be evaluated for their ability to: i) opsonize the bacteria, facilitating its phagocytosis by the immune system, ii) prevent bacterial adhesion and cellular invasion, and iii) interfere with K. pneumoniae biofilm formation and iv) prevent or reduce bladder changes associated with the infection. Protection will be determined by quantifying bacteria recovered from the kidneys and bladder of vaccinated versus control animals, alongside analysis of local inflammatory response and voiding profile. The results of this research will contribute to the development of prophylactic options against K. pneumoniae infections. (AU)