Lipopolysaccharide as an Antigen Target for the Formulation of a Universal Vaccine againstEscherichia coliO111 Strains

Abstract

A promising approach to developing a vaccine against O111 strains of diarrheagenic Escherichia coli that exhibit different mechanisms of virulence is to target either the core or the polysaccharide chain (O antigen) of their lipopolysaccharide (LPS). However, due to structural variations found in both these LPS components, to use them as antigen targets for vaccination, it is necessary to formulate a vaccine able to induce a humoral immune response that can recognize all different variants found in E. coli O111 strains. In this study, it was demonstrated that, despite differences in composition of oligosaccharide repeat units between O111ab and O111ac LPS subtypes, antibodies against one O111 subtype can recognize and inhibit the adhesion to human epithelial cells of all categories of O111 E. coli (enteropathogenic E. coli [EPEC], enterohemorrhagic E. coli [EHEC], and enteroaggregative E. coli [EAEC]) strains regardless of the nature of their flagellar antigens, mechanisms of virulence, or O111 polysaccharide subtypes. These antibodies were also able to increase the clearance of different strains of O111 E. coli by macrophages. PCR analyses of the pathways involved in O111 LPS core biosynthesis showed that all EAEC strains have core type R2, whereas typical EPEC and EHEC have core type R3. In contrast, atypical EPEC strains have core types R2 and R3. In summary, the results presented herein indicate that the O111 polysaccharide and LPS core types R2 and R3 are antigen targets for panspecific immunotherapy against all categories of O111 E. coli.

Sequencing a piece of history: complete genome sequence of the original Escherichia coli strain

“…The biological significance of the R2 core is unknown: it is the least frequently occurring core type amongst commensal and pathogenic E. coli [22]. However, the presence of an R2 oligosaccharide core in a commensal organism suggests that efforts to target vaccines to this core region might be unwise, as it might negatively impact on the ability of a commensal organism to colonize the gut [23]. …”

Challenges for Clinical Development of Vaccines for Prevention of Hospital-Acquired Bacterial Infections

“…Immunological strain variability limits cross-reactivity of the immune response to variable surface proteins and polysaccharides and undermines vaccine-mediated cross-protection against strains not included in the vaccine design. The lack of cross-protectivity has hindered the development of vaccines against several ESCAPE pathogens: (33,34). To avoid toxicity in these vaccines O111 LPS was conjugated to carrier proteins.…”

“…Strain-specific LPS (O-glycan)-based developments of monoclonal antibodies targeting K. pneumoniae strains such as ST258 and E. coli strains ST131 ( 30 – 32 ) have been developed to protect from epidemic strains with high transmission potential, antibiotic resistance and severe disease manifestation. Notably, serotype-specific vaccines have also been proposed for targeting O111 E. coli due to this serotype's high representation in toxin producing E. coli (EHEC, STEC, EPEC, and EAEC) ( 33 , 34 ). To avoid toxicity in these vaccines O111 LPS was conjugated to carrier proteins.…”

Resposta imune induzida por uma vacina conjugada contra Escherichia coli diarreiogênicas pertencentes ao sorogrupo O111.

“…Resultados obtidos no Laboratório de Bacteriologia do Instituto Butantan mostraram que anticorpos contra o polissacarídeo O111 foram capazes de inibir a adesão de todas as categorias de E. coli pertencentes a esse sorogrupo. Em acréscimo, esses anticorpos também aumentaram a fagocitose de E. coli O111 por macrófagos na presença de complemento(SANTOS et al, 2010). Esses resultados indicam que o polissacarídeo O111 é um bom candidato a antígeno para formulação de uma vacina contra todas as cepas de E. coli pertencentes ao sorogrupo O111.Todavia, polissacarídeos O111 são antígenos Timo independente do tipo II e, portanto, não induzem altos níveis de anticorpos ou memória imunológica em crianças menores de 2 anos de idade, cuja maior parte dos linfócitos B são imaturos…”