Provided are methods of mitigating, reversing or eliminating in a subject one or more symptoms associated with cognitive impairment associated with amyloid deposits in the brain (e.g., olfactory dysfunction as a risk factor of dementia, mild cognitive impairment, Alzheimer's Disease) by detecting and targeting gram negative bacteria in the brain.

The present invention relates to a synthetic saccharide of general formula (I) that is related to Klebsiella pneumoniae serotype O1, O2, O2ac, and O8 O-polysaccharide and carbapenem-resistant Klebsiella pneumoniae ST258 O-polysaccharide and conjugate thereof. Said synthetic saccharide, said conjugate and pharmaceutical composition containing said synthetic saccharide or said conjugate are useful for prevention and/or treatment of diseases associated with Klebsiella pneumoniae. Furthermore, the synthetic saccharide of general formula (I) is useful as marker in immunological assays for detection of antibodies against Klebsiella pneumoniae bacteria.

Compositions and methods are described for inducing an immune response against extra-intestinal pathogenic Escherichia coli (ExPEC) to thereby provide immune protection against diseases associated with ExPEC. In particular, compositions and methods are described for using conjugates of E. coli polysaccharide antigens O25B, O1A, O2, and O6A covalently bound to a detoxified exotoxin A of Pseudomonas aeruginosa (EPA) carrier protein as vaccines for the prevention of invasive ExPEC disease caused by ExPEC serotypes O1A, O2, O6A and O25B.

The invention pertains to host cells for producing a bioconjugate of an E. coli O18 antigen polysaccharide conjugated to a carrier protein. The host cells are characterized in that they comprise modified Wzy O-antigen polymerases with specific combinations of amino acid substitutions in one or more of positions 199, 377 and 395 as compared to the wild type Wzy O-antigen polymerase of SEQ ID NO: 1, which modified Wzy O-antigen polymerases improve the yield and glycosylation pattern of the O18 bioconjugates produced by the host cells. The invention further relates to methods wherein the host cells are used to produce a bioconjugate of an E. coli O18 antigen polysaccharide conjugated to a carrier protein, compositions comprising these bioconjugates, including multivalent compositions comprising bioconjugates of additional O antigen polysaccharide-serotypes.

The disclosure relates to polypeptides and pharmaceutical compositions comprising polypeptides that find use in the prevention or treatment of cancer, in particular breast cancer, ovarian cancer and colorectal cancer. The disclosure also relates to methods of inducing a cytotoxic T cell response in a subject or treating cancer by administering pharmaceutical compositions comprising the peptides, and companion diagnostic methods of identifying subjects for treatment. The peptides comprise T cell epitopes that are immunogenic in a high percentage of patients.

An improved heroin conjugate vaccine is detailed; to accomplish this task the systematic exploration of twenty vaccine formulations with varying combinations of carrier proteins and adjuvants were undertaken. In regard to adjuvants, a Toll-like receptor 9 (TLR9) agonist and a TLR3 agonist in the presence of alum were explored. The vaccine formulations containing TLR3 or TLR9 agonist alone-elicited strong anti-heroin antibody titers and blockade of heroin-induced antinociception when formulated with alum; however, a combination of TLR3 and 9 adjuvants did not result in improved efficacy. Investigation of stability of the two lead formulations revealed that the TLR9 but not the TLR3 formulation was stable when stored over 30 days. Furthermore, mice immunized with the TLR9+alum heroin vaccine gained significant protection from lethal heroin doses, suggesting that this vaccine formulation is suitable for mitigating the lethal effects of heroin, even following long-term storage at room temperature.

The present disclosure relates to extracellular vesicles (EVs) that are capable of targeting a cell in the CNS of a subject. Also provided herein are methods for producing the EVs and methods for using the EVs to treat and/or prevent diseases or disorders of the CNS (e.g., neurological disorders).

The present invention provides capsular polysaccharides from Streptococcus pneumoniae serotypes identified using NMR. The present invention further provides polysaccharide-protein conjugates in which capsular polysaccharides from one or more of these serotypes are conjugated to a carrier protein such as CRM197. Polysaccharide-protein conjugates from one or more of these serotypes may be included in multivalent pneumococcal conjugate vaccines having polysaccharides from multiple additional Streptococcus pneumoniae serotypes.

The present invention provides capsular polysaccharides from Streptococcus pneumoniae serotypes identified using NMR The present invention further provides polysaccharide-protein conjugates in which capsular polysaccharides from one or more of these serotypes are conjugated to a carrier protein such as CRM197. Polysaccharide-protein conjugates from one or more of these serotypes may be included in multivalent pneumococcal conjugate vaccines having polysaccharides from multiple additional Streptococcus pneumoniae serotypes.

The present invention provides a conjugate comprising an albumin binding peptide and a cargo, compositions for directing cargos to the lymphatic system, and vaccines. The methods of the invention can be used to increase an immune response, or to treat cancer or an infectious disease.