This invention relates to the medical use of pathogen associated molecular pattern (PAMP) displaying immunostimulatory microbial immuno-adjuvants [MIAs], as therapeutics when used in combination with check point inhibitors to treat various types of cancer and to methods of treatment which involve treating a subject with these compounds and compound mixtures and process methods for identifying and optimally composing them for their therapeutic use in cancer treatment. It also relates to the use of inhibitors of these PAMP displaying immunostimulatory microbial immuno-adjuvants [MIAs], as therapeutics when used to treat inflammatory bowel disease (IBD) including Crohn's Disease and ulcerative colitis and irritable bowel syndrome (IBS) and process methods for identifying and optimally composing them for their therapeutic use in IBD and IBS.

Described herein are methods of inserting nucleic acid sequences into host cells. Also described herein are genetically stable host cells comprising inserted nucleic acid sequences and methods of using such host cells in the generation of proteins.

The invention relates to gram-negative bacteria carrying gene-inactivating mutations that cause deletion of proteins belonging to the OMV proteome, to Outer Membrane Vesicles (OMVs) produced by these bacteria and immunogenic compositions thereof.

A Shigella flexneri O-antigen of a first serotype or subserotype are provided for use in raising an immune response against one or more Shigella flexneri O-antigen of a different serotype or subserotype, together with associated binding moieties, pharmaceutical compositions, kits, uses or methods.

Disclosed is the attenuated Salmonella typhi vaccine Ty21a utilized as a vector for Shigella and/or enterotoxogenic E. coli genes stably integrated in the Ty21a chromosome. These genes include a heterologous Shigella sonnei O-antigen biosynthetic gene region that comprises the wzz gene and expresses Shigella sonnei form 1 O-antigen, as well as a heterologous acid resistance biosynthetic gene system comprising a YbaS gene, which enables increased stability of the Ty21a vector at pH 2.5 relative to Ty21a without the integrated acid resistance biosynthetic gene system.

The present disclosure provides a cell-free method for synthesizing an Invasion Plasmid Antigen B (IpaB) antigen associated with a Shigella bacterium comprising exogenous addition of the purified chaperone protein IpgC to the cell-free synthesis mixture. The disclosure further provides IpaB antigen mutants comprising non-natural amino acids incorporated during cell-free synthesis, enabling covalent conjugation to a Shigella O-antigen polysaccharide. Further provided are Ipa B antigens and conjugates thereof, as well as immunogenic compositions prepared with the synthesized IpaB antigens and conjugates thereof and methods of use.

Described herein are methods of inserting nucleic acid sequences into host cells. Also described herein are genetically stable host cells comprising inserted nucleic acid sequences and methods of using such host cells in the generation of proteins.

The present disclosure provides immunogenic compositions comprising Group A Streptococcus (GAS) polypeptide antigens and at least one polypeptide-polysaccharide conjugate. The present disclosure further provides methods of using such compositions to induce immune responses against GAS infections in subjects.

Heptose-1-monophosphate-7-derivatives are modifiable immunomodulators that can be used to prepare clinically active conjugate compounds. Such conjugate compounds are useful in modulating an immune response in a subject.

A composition comprising Shigella-Tetravalent (4-valent Shigella) bioconjugates. That encompasses the Shigella O-polysaccharide antigens of serotypes Shigella flexneri 2a, 3a, 6 and Shigella sonnei covalently linked to the protein carrier.