Preclinical Immunogenicity and Efficacy of Optimized O25b O-Antigen Glycoconjugates To Prevent MDR ST131 E. coli Infections.

Multivalent O-antigen polysaccharide glycoconjugate vaccines are under development to prevent invasive infections caused by pathogenic . Sequence type 131 (ST131) Escherichia coli of serotype O25b has emerged as the predominant lineage causing invasive multidrug-resistant extraintestinal pathogenic E. coli (ExPEC) infections.

Molecular epidemiology and expression of capsular polysaccharides in Staphylococcus aureus clinical isolates in the United States.

Staphylococcus aureus capsular polysaccharides (CP) are important virulence factors under evaluation as vaccine antigens. Clinical S. aureus isolates have the biosynthetic capability to express either CP5 or CP8 and an understanding of the relationship between CP genotype/phenotype and S.

Bactericidal activity of sera from adolescents vaccinated with bivalent rLP2086 against meningococcal serogroup B outbreak strains from France.

Objectives: Bivalent rLP2086 (Trumenba®; MenB-FHbp), composed of two factor H binding proteins (FHbps), is a vaccine approved in the United States for prevention of Neisseria meningitidis serogroup B (MnB) invasive meningococcal disease (IMD). Bactericidal activity of sera from subjects vaccinated with bivalent rLP2086 was assessed against MnB isolates from recent disease outbreaks in France.

Methods: MnB isolates from IMD cases were characterized by whole genome sequencing and FHbp expression was assessed using a flow cytometry-based assay.

Meningococcal serogroup B vaccines: Estimating breadth of coverage.

Neisseria meningitidis serogroup B (MenB) is an important cause of invasive meningococcal disease. The development of safe and effective vaccines with activity across the diversity of MenB strains has been challenging. While capsular polysaccharide conjugate vaccines have been highly successful in the prevention of disease due to meningococcal serogroups A, C, W, and Y, this approach has not been possible for MenB owing to the poor immunogenicity of the MenB capsular polysaccharide.

Neisseria meningitidis Serogroup B Vaccine, Bivalent rLP2086, Induces Broad Serum Bactericidal Activity Against Diverse Invasive Disease Strains Including Outbreak Strains.

Background: Bivalent rLP2086 (Trumenba), 1 of 2 meningococcal serogroup B (MnB) vaccines recently approved in the United States for the prevention of MnB disease in individuals 10-25 years of age, is composed of 2 lipidated factor H binding proteins from subfamilies A and B. This study evaluated the breadth of MnB strain coverage elicited by bivalent rLP2086 measured with serum bactericidal assays using human complement (hSBAs).

Methods: hSBA responses to diverse MnB clinical strains circulating in the United States and Europe (n = 23), as well as recent US university outbreak strains (n = 4), were evaluated.

High Resolution Mapping of Bactericidal Monoclonal Antibody Binding Epitopes on Staphylococcus aureus Antigen MntC.

The Staphylococcus aureus manganese transporter protein MntC is under investigation as a component of a prophylactic S.aureus vaccine. Passive immunization with monoclonal antibodies mAB 305-78-7 and mAB 305-101-8 produced using MntC was shown to significantly reduce S.

Comparison of Phenotypic and Genotypic Approaches to Capsule Typing of Neisseria meningitidis by Use of Invasive and Carriage Isolate Collections.

Neisseria meningitidis serogroup B (MnB) is a leading cause of bacterial meningitis; however, MnB is most commonly associated with asymptomatic carriage in the nasopharyngeal cavity, as opposed to the disease state. Two vaccines are now licensed for the prevention of MnB disease; a possible additional benefit of these vaccines could be to protect against disease indirectly by disrupting nasopharyngeal carriage (e.g.

Regulation of Staphylococcus aureus MntC expression and its role in response to oxidative stress.

Staphylococcus aureus is a successful human pathogen that has developed several approaches to evade the immune system, including resistance strategies to prevent oxidative killing by immune cells. One mechanism by which this evasion occurs is by production of superoxide dismutase enzymes, which require manganese as a cofactor. Manganese is acquired by the manganese transporter MntABC.

Capsular polysaccharides are an important immune evasion mechanism for Staphylococcus aureus.

Staphylococcus aureus can cause severe life threatening invasive diseases. The principal immune effector mechanism by which humans are protected from Gram positive bacteria such as S. aureus is antigen specific antibody- and complement-dependent opsonophagocytosis.

A recombinant clumping factor A-containing vaccine induces functional antibodies to Staphylococcus aureus that are not observed after natural exposure.

Staphylococcus aureus is a Gram-positive pathogen that causes devastating disease and whose pathogenesis is dependent on interactions with host cell factors. Staphylococcal clumping factor A (ClfA) is a highly conserved fibrinogen (Fg)-binding protein and virulence factor that contributes to host tissue adhesion and initiation of infection. ClfA is being investigated as a possible component of a staphylococcal vaccine.

The catalytic flexibility of tRNAIle-lysidine synthetase can generate alternative tRNA substrates for isoleucyl-tRNA synthetase.

Bacteria decode the isoleucine codon AUA using a tRNA species that is posttranscriptionally modified at the wobble position of the anticodon with a lysine-containing cytidine derivative called lysidine. The lysidine modification of tRNA(Ile2) is an essential identity determinant for proper aminoacylation by isoleucyl tRNA synthetase (IleRS) and codon recognition on the ribosome. The ATP- and lysine-dependent formation of lysidine is catalyzed by tRNA(Ile)-lysidine synthetase.