Abstract: The present invention relates hydroxypyridoxazepine compounds, methods of making them, pharmaceutical compositions containing them and their use as Nrf2 activators. In particular, the invention relates to compounds of Formula (I), and pharmaceutically acceptable salts thereof, or a tautomer thereof, or a hydrate thereof.

Abstract: The present invention is directed to a bioconjugate vaccine, such as an O 1-bioconjugate vaccine, comprising: a protein carrier comprising a protein carrier containing at least one consensus sequence, DIE-X-N-Z-S/T, wherein X and Z may be any natural amino acid except proline; at least one antigenic polysaccharide from at least one pathogenic bacterium, linked to the protein carrier; and, optionally, an adjuvant. In another aspect, the present invention is directed to a method of producing an O 1-bioconjugate in a bioreactor comprising a number steps.

Abstract: The disclosure provides synthetic (e.g. recombinant) pneumococcal saccharide comprising one or more repeat unit(s) ?4)-?-D-Glcp-(1?3)-[[?-L-Rhap-(1?2)]-[Gro-(2?P?3)]-?-D-Galp-(1?4)]-?-L-Rhap-(1?. Also provided are conjugates comprising a ?4)-?-D-Glcp-(1?3)-[[?-L-Rhap-(1?2)]-[Gro-(2?P?3)]-?-D-Galp-(1?4)]-?-L-Rhap-(1?, immunogenic compositions, vaccines and their use in preventing or treating infection by Streptococcus pneumoniae.

Abstract: The inventors have identified residues within variant 2 and variant 3 of meningococcal fHpb which can be modified to enhance their properties.

Abstract: A simian adenoviral vector comprising two expression cassettes, wherein each expression cassette comprises a transgene and a promoter, and wherein the first expression cassette is inserted in the E1 region of the simian adenoviral vector, and the second expression cassette is inserted in a region of the adenoviral vector that is compatible with vector replication.

Abstract: The present invention relates to administration regimens which are particularly suited for vaccine composition comprising polynucleotides which encode immunogenic polypeptides. Said administration regimens involve the repeated administration of a vaccine composition and enhance the immune response against the immunogenic polypeptide.

Abstract: The present invention relates to a nucleic acid encoding a HSV2 Fc receptor or immunogenic fragment or variant thereof for use in generating a cross reactive immune response against HSV1 in a subject. Also provided is a nucleic acid encoding a HSV1 Fc receptor or immunogenic fragment or variant thereof for use in generating a cross reactive immune response against HSV2 when administered to a subject.

Abstract: Modified meningococcal fHbp polypeptides with increased stability.

Abstract: Described are mutant human cytomegalovirus (HCMV) pentamer complex polypeptides, methods of making them, and their use in HCMV protein complexes and compositions. In particular, the use of the modified HCMV polypeptides to stabilize HCMV complexes or unmask a pentamer epitope is described.

Abstract: A bioconjugate of an E. coli glucosylated O4 antigen polysaccharide covalently linked to a carrier protein and compositions thereof are provided. Also provided are recombinant host cells for producing the bioconjugate, and methods of producing the bioconjugate using the recombinant host cells. The recombinant host cells contain a nucleic acid encoding a glucosyl transferase capable of modifying the E. coli O4 antigen with glucose branching to produce the glucosylated O4 antigen polysaccharide. Bioconjugates of an E. coli glucosylated O4 antigen polysaccharide described herein can be used alone or in combination with one or more additional E. coli O-antigen polysaccharides to induce antibodies against an E. coli glucosylated antigen, and to vaccinate a subject against extra-intestinal pathogenic E. coli (ExPEC).

Abstract: Compounds of formula (I) are described, wherein each of the variable groups is as defined in the specification. Also described are pharmaceutical compositions containing a compound of formula (I), and uses of the compounds and pharmaceutical compositions for inhibiting Nav1.8 voltage-gated sodium channels and treating Nav1.8 mediated diseases, disorders, and conditions, such as pain and pain-associated diseases, disorders, and conditions and cardiovascular diseases, disorders, and conditions, such as atrial fibrillation.

Abstract: This invention generally relates to immunogenic compositions that comprise an RNA component and a polypeptide component. Immunogenic compositions that deliver antigens in two different forms—a first antigen from a pathogen, in RNA-coded form; and a second antigen from a different pathogen, in polypeptide form—are effective in inducing immune response to both pathogens.

Abstract: The invention provides Epstein-Barr Virus antigen polynucleotides, polypeptides and vectors; as well as immunogenic compositions comprising the same. It includes the use of Epstein-Barr Virus antigen constructs to produce vaccines for treating and preventing Epstein-Barr Virus infections and Epstein-Barr Virus-associated diseases, such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus.

Abstract: The invention relates to an expression system comprising polynucleotides encoding proteins, wherein the expression system comprises a first polynucleotide encoding at least one protein, peptide or variant thereof, which induces a T cell response, and a second polynucleotide encoding at least one protein, peptide or variant thereof, which induces an anti-pathogenic B cell response. The invention further relates to protein mixtures encoded by the expression system and cells comprising the expression system or the protein mixture and pharmaceutical compositions comprising the expression system or the protein mixture.

Abstract: The present invention is directed to a nucleic acid suitable for use in treatment or prophylaxis of an infection with a coronavirus, preferably with a Coronavirus SARS-CoV-2, or a disorder related to such an infection, preferably COVID-19. The present invention is also directed to compositions, polypeptides, and vaccines. The compositions and vaccines preferably comprise at least one of said nucleic acid sequences, preferably nucleic acid sequences in association a lipid nanoparticle (LNP). The invention is also directed to first and second medical uses of the nucleic acid, the composition, the polypeptide, the combination, the vaccine, and the kit, and to methods of treating or preventing a coronavirus infection, preferably a Coronavirus infection.

Abstract: Provided is RNA encoding an immunogen is delivered to a large mammal at a dose of from 5 ?g to 100 ?g or at a dose between 0.1 ?g per kilogram body mass of the large mammal and 1.5 ?g per kilogram body mass of the large mammal. Provided is a method of raising an immune response in a large mammal, comprising administering to the large mammal a dose of from 5 ?g to 100 ?g or a dose of between 0.1 ?g of RNA encoding the immunogen per kilogram body mass of the large mammal and 1.5 ?g of RNA encoding the immunogen per kilogram body mass of the large mammal. The delivered RNA can elicit an immune response in the large mammal.

Abstract: RNA encoding an immunogen is delivered to a large mammal at a dose of between 2 ?g and 100 ?g. Thus the invention provides a method of raising an immune response in a large mammal, comprising administering to the mammal a dose of between 2 ?g and 100 ?g of immunogen-encoding RNA. Similarly, RNA encoding an immunogen can be delivered to a large mammal at a dose of 3 ng/kg to 150 ng/kg. The delivered RNA can elicit an immune response in the large mammal.

Abstract: The invention relates to compounds of Formula (I), (Ia), (Ib), (II) or (III), salts thereof, pharmaceutical compositions thereof, as well as therapeutic methods of treatment and prevention.

Abstract: This invention generally relates to immunogenic compositions that comprise an RNA component and a polypeptide component. Immunogenic compositions that deliver antigens in two different forms—a first antigen from a pathogen, in RNA-coded form; and a second antigen from a different pathogen, in polypeptide form—are effective in inducing immune response to both pathogens.

Abstract: RNA encoding an immunogen is delivered to a large mammal at a dose of between 2 ?g and 100 ?g. Thus, the invention provides a method of raising an immune response in a large mammal, comprising administering to the mammal a dose of between 2 ?g and 100 ?g of immunogen-encoding RNA. Similarly, RNA encoding an immunogen can be delivered to a large mammal at a dose of 3 ng/kg to 150 ng/kg. The delivered RNA can elicit an immune response in the large mammal.