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.

This disclosure relates to the design of E. coli mutated FimH polypeptides that result in improved biochemical properties and immunogenicity, compositions comprising such polypeptides, and uses thereof.

The present invention relates to a pharmaceutical composition comprising a modified mRNA that is stabilised by sequence modifications and optimised for translation. The pharmaceutical composition according to the invention is particularly well suited for use as an inoculating agent, as well as a therapeutic agent for tissue regeneration. In addition, a process is described for determining sequence modifications that promote stabilisation and translational efficiency of modified mRNA of the invention.

The present disclosure belongs to the technical field of veterinary biological products, and specifically relates to a triple vaccine for diseases caused by Salmonella typhimurium, Riemerella anatipestifer and Escherichia coli. In the triple vaccine, antigens are an inactivated Salmonella typhimurium E01 strain, an inactivated Riemerella anatipestifer R01 strain and an inactivated Escherichia coli E01 strain. The three strains used in the vaccine have high virulence, disable immunogenicity and disable cross-protection. The prepared vaccine has a desirable safety, causing no local or systemic adverse reactions. In a shelf life test, all indicators of the vaccine are stable and effective after a data analysis of traits, a safety test and an efficacy test; in addition, efficacy test results prove that the inactivated triple vaccine can produce desirable antibodies and relatively desirable attacking protection.

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.

Disclosed are a bacteriologically-modified whole-cell tumor vaccine and a method of making the same. The method includes: lysing bacteria at logarithmic growth phase to obtain a bacterial lysate; mixing the bacterial lysate with an excessive amino compound solution to aminate the bacterial lysate in the presence of EDC; mixing the aminated bacterial lysate with the tumor cells for a certain period of time to produce bacteriologically-modified tumor cells; and inactivating the bacteriologically-modified tumor cells to produce the bacteriologically-modified whole-cell tumor vaccine. The bacteriologically-modified whole-cell tumor vaccine has been demonstrated to have desirable therapeutic effect in tumor model mice.

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.

In one aspect, the invention relates to an immunogenic composition comprising modified O-polysaccharide molecules derived from E. coli lipopolysaccharides and conjugates thereof. Multivalent vaccines may be prepared by combining two or more monovalent immunogenic compositions for different E. coli serotypes. In one embodiment, the modified O-polysaccharide molecules are produced by a recombinant bacterium that includes a wzz gene.

Methods of producing a pathogen with reduced replicative fitness are disclosed, as are attenuated pathogens produced using the methods. In particular examples, the method includes deoptimizing one or more codons in a coding sequence, thereby reducing the replicative fitness of the pathogen. Methods of using the attenuated pathogens as immunogenic compositions are also disclosed.

The present disclosure describes multivalent antibacterial vaccines for the treatment of bacterial infections, such as Klebsiella, E. coli and E. cloacae, as well as therapy-resistant forms thereof.