PRODUCTION ANDA IMMUNOLOGICAL EVALUATION OF MULTI-EPITOPE VACCINES BASED ON FIMBRIAL COMPONENTS OF Klebsiella pneumoniae

• Grant number: 25/06027-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: December 01, 2025
• End date: July 31, 2030
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Michelle Darrieux Sampaio Bertoncini
• Grantee: Isabelle Barbosa Ciaparin
• 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 bacterium associated with severe nosocomial infections, such as ventilator-associated pneumonia, urinary tract infections, and sepsis. The emergence of multidrug-resistant strains, particularly to the carbapenem class, has led to its inclusion on the World Health Organization's (WHO) list of critical priority pathogens, highlighting the urgent need for new preventive strategies. In this context, vaccine development has emerged as a promising alternative to conventional antibiotic therapy. Type I and type III fimbriae, structures involved in host cell adhesion, biofilm formation, and immune evasion, represent relevant vaccine targets. This project aims to develop and immunologically characterize multiepitope vaccine formulations based on fimbrial components of K. pneumoniae. The proposed approach involves the rational selection of B and T cell epitopes, based on in silico predictions, derived from the FimH, FimA, MrkD, and MrkA proteins. These epitopes will be incorporated into chimeric constructs, whose recombinant proteins will be expressed, purified, and used to immunize mice. In parallel, the FimA and MrkA subunits will be produced individually, as well as fusion type I (FimH-FimA) and type III (MrkD-MrkA) fimbriae hybrids, for comparative purposes. Specific antibody titers, complement system activation, opsonophagocytic efficacy, and cytokine profiles will be evaluated. Functional assays will also be conducted to assess the role of fimbriae in bacterial adhesion to respiratory epithelium and in biofilm formation. It is expected that the results will contribute to the development of innovative, safe, and effective vaccines against K. pneumoniae, with potential application in combating infections caused by multidrug-resistant strains. (AU)