Strain Selection for Generation of O-Antigen-Based Glycoconjugate Vaccines against Invasive Nontyphoidal Salmonella Disease

摘要: Nontyphoidal Salmonellae, principally S. Typhimurium and Enteritidis, are a major cause of invasive bloodstream infections in sub-Saharan Africa with no vaccine currently available. Conjugation lipopolysaccharide O-antigen to carrier protein constitutes promising vaccination strategy. Here we describe rational process select the most appropriate isolates Salmonella as source for developing bivalent glycoconjugate vaccine. We screened library 30 21 Enteritidis order identify suitable strains large scale production generation conjugate vaccines. Initial screening was based on growth characteristics, safety profile isolates, production, characteristics terms molecular size, O-acetylation glucosylation level position, determined by phenol sulfuric assay, NMR, HPLC-SEC HPAEC-PAD. Three animal each serovar were identified used synthesize candidate vaccines, using CRM197 protein. The immunogenicity these conjugates functional activity induced antibodies investigated ELISA, serum bactericidal assay flow cytometry. showed high structural diversity, including rhamnose Malawian strain generating specific immunodominant epitope. provoked an anti-O-antigen response primarily against O:5 determinant. from structurally more homogeneous than Typhimurium, idiosyncratic antibody responses detected conjugates. Of three initially selected two (1418 2189) (502 618) generated glycoconjugates able induce levels breadth serovar-specific coverage, use production. selection approach described is potentially applicable development vaccines other bacterial pathogens.