In-silico and experimental analysis of Klebsiella pneumoniae fimbriae subunits for vaccine development

Autor(es):Mostrar menos -

Assoni, Lucas ; Valim, Vitoria ; Couto, Ana Julia Melo ; Trentini, Monalisa ; Goncalves, Viviane Maimoni ; Ferraz, Lucio Fabio Caldas ; Sciani, Juliana Mozer ; Cremonesi, Aline Sampaio ; Converso, Thiago R. ; de Carvalho, Lucas Miguel ; Darrieux, Michelle

• Tipo de documento: Artigo Científico
• Fonte: Vaccine; v. 53, p. 11-pg., 2025-04-19.

Resumo

Klebsiella pneumoniae infections pose a great burden worldwide, causing high morbidity and mortality. New therapeutic/prophylactic strategies are urgently needed to overcome antibiotic resistance and reduce the health and economic impacts of diseases caused by this pathogen. Fimbriae are important virulence factors involved in biofilm formation and adhesion to host cells. Their exposed location and conservation among clinical isolates make them interesting candidates for inclusion in protein-based vaccines. Therefore, the present work investigated the immunological potential of K. pneumoniae fimbriae subunits as vaccine candidates. In-silico analysis of the type 1 (FimA and FimH) and type 3 (MrkA and MrkD) fimbrial components showed that all four proteins contain B-and T-cell epitopes predicted to bind into the peptide binding cleft. Additionally, a 7-allele prediction model was used to assess the binding and presentation of these epitopes, with some showing potential for presentation across different class II MHC alleles. The genes encoding fimbriae subunits FimA and MrkA were cloned in prokaryotic vector systems, expressed in E. coli and purified by Ni2+ affinity chromatography. Subcutaneous immunization of mice with recombinant FimA and MrkA using Alum as adjuvant induced specific IgG production. The protective potential of MrkA immunization was tested against challenge with a hypervirulent K. pneumoniae strain; although a modest increase in survival time was observed in the immunized group, all mice died within 5 days of infection. Overall, although the in-silico analysis suggests that K. pneumoniae fimbriae components promising vaccine candidates, protection against highly virulent strains with increased capsule may require additional antigens. (AU)

• Processo FAPESP: 23/10579-8 - AVALIAÇÃO DE SUBUNIDADES DAS FIMBRIAS TIPOS I E III COMO CANDIDATOS VACINAIS CONTRA INFECÇÃO POR Klebsiella pneumoniae
• Beneficiário: Michelle Darrieux Sampaio Bertoncini
• Modalidade de apoio: Auxílio à Pesquisa - Regular