Abstract: The invention pertains to a complex of an OMV, a vertebrate antimicrobial peptide (AMP) and an antigen, wherein the AMP is non-covalently complexed with the OMV and wherein the antigen is conjugated to the AMP. Preferably, the antigen is covalently linked to the AMP. The invention further concerns the induction of an immune response using the complex of the invention as well as a method for producing the complex of the invention.

Abstract: The present invention relates to neisserial LPS having a hexa-acylated lipid A moiety, wherein the hexa-acylated lipid A moiety is modified as compared to the lipid A moiety of a wild-type neisserial LPS in that it comprises a palmitoleoyl instead of a lauroyl secondary acyl chain on the glucosamine at the non-reducing end of the lipid A moiety. The invention further relates to mixtures of the hexa-acylated LPS with the corresponding penta-acylated LPS, lacking a secondary acyl chain on the glucosamine at the non-reducing end of the lipid A moiety. The invention also relates to neisserial bacteria that have been genetically modified to reduce expression of the endogenous 1pxL1 gene and to introduce expression of a heterologous thermosensitive 1pxP gene for producing the hexa- and penta-acylated LPS.

Abstract: The present invention relates to neisserial LPS having a tetra-acylated lipid A moiety, wherein the tetra-acylated lipid A moiety is modified as compared to the lipid A moiety of a wild-type neisserial LPS in that it lacks one of the secondary acyl chains and lacks a primary acyl chain on the 3-position of the glucosamine at the reducing end of the lipid A moiety. The invention further relates to neisserial bacteria that have been genetically modified to reduce expression of either one of the endogenous lpxL1 or lpxL2 genes and to introduce expression of a heterologous pagL gene. The neisserial LPS of the invention has TLR4 agonist properties and is therefore useful in compositions for inducing or stimulating immune responses, such as vaccines, as well as in other forms of immunotherapy.

Abstract: The present invention relates to neisserial LPS having a hexa-acylated lipid A moiety, wherein the hexa-acylated lipid A moiety is modified as compared to the lipid A moiety of a wild-type neisserial LPS in that it comprises a palmitoleoyl instead of a lauroyl secondary acyl chain on the glucosamine at the non-reducing end of the lipid A moiety. The invention further relates to mixtures of the hexa-acylated LPS with the corresponding penta-acylated LPS, lacking a secondary acyl chain on the glucosamine at the non-reducing end of the lipid A moiety. The invention also relates to neisserial bacteria that have been genetically modified to reduce expression of the endogenous lpxL1 gene and to introduce expression of a heterologous thermosensitive lpxP gene for producing the hexa- and penta-acylated LPS.

Abstract: The current invention lies in the field of medicine and more specifically in the field of vaccinology. The current invention concerns a novel Bordetella LPS and a modified bacterium of the genus Bordetella comprising such modified LPS. The LPS of the invention has a reduced endotoxicity in comparison to an unmodified Bordetella LPS. The modified LPS of the invention is therefore particularly suitable for use in inducing or stimulating an immune response in a subject, wherein the immune response is induced or stimulated against a Bordetella infection. The modified Bordetella LPS of the invention is obtainable by introducing in a Bordetella cell the expression of a heterologous acyl transferase. In particular, the modified Bordetella cell of the invention has an increased expression of an heterologous LpxA, LpxL or LpxD acyl transferase.

Abstract: The present invention relates to neisserial LPS having a tetra-acylated lipid A moiety, wherein the tetra-acylated lipid A moiety is modified as compared to the lipid A moiety of a wild-type neisserial LPS in that it lacks one of the secondary acyl chains and lacks a primary acyl chain on the 3-position of the glucosamine at the reducing end of the lipid A moiety. The invention further relates to neisserial bacteria that have been genetically modified to reduce expression of either one of the endogenous lpxL1 or lpxL2 genes and to introduce expression of a heterologous pagL gene. The neisserial LPS of the invention has TLR4 agonist properties and is therefore useful in compositions for inducing or stimulating immune responses, such as vaccines, as well as in other forms of immunotherapy.

Abstract: The present invention relates to vaccine compositions based on Gram-negative outer membrane vesicles displaying antigens of pathogens expressed as part of a fusion protein comprising N-terminal parts of surface expressed lipoproteins of Gram-negative bacteria, and use of such compositions in vaccination. The invention further relates to the fusion lipoproteins comprising N-terminal parts of surface expressed lipoproteins of Gram-negative bacteria and antigens of pathogens fused thereto, DNA constructs and bacterial host cells for expressing these fusion lipoproteins and to methods for producing outer membrane vesicles displaying the fusion lipoproteins.

Abstract: The present invention relates to vaccine compositions based on Gram-negative outer membrane vesicles displaying antigens of pathogens expressed as part of a fusion protein comprising N-terminal parts of surface expressed lipoproteins of Gram-negative bacteria, and use of such compositions in vaccination. The invention further relates to the fusion lipoproteins comprising N-terminal parts of surface expressed lipoproteins of Gram-negative bacteria and antigens of pathogens fused thereto, DNA constructs and bacterial host cells for expressing these fusion lipoproteins and to methods for producing outer membrane vesicles displaying the fusion lipoproteins.

Abstract: The present invention relates to vaccine compositions based on Gram-negative outer membrane vesicles displaying antigens of pathogens expressed as part of a fusion protein comprising N-terminal parts of surface expressed lipoproteins of Gram-negative bacteria, and use of such compositions in vaccination. The invention further relates to the fusion lipoproteins comprising N-terminal parts of surface expressed lipoproteins of Gram-negative bacteria and antigens of pathogens fused thereto, DNA constructs and bacterial host cells for expressing these fusion lipoproteins and to methods for producing outer membrane vesicles displaying the fusion lipoproteins.

Abstract: The current invention lies in the field of medicine and more specifically in the field of vaccinology. The current invention concerns a novel Bordetella LPS and a modified bacterium of the genus Bordetella comprising such modified LPS. The LPS of the invention has a reduced endotoxicity in comparison to an unmodified Bordetella LPS. The modified LPS of the invention is therefore particularly suitable for use in inducing or stimulating an immune response in a subject, wherein the immune response is induced or stimulated against a Bordetella infection. The modified Bordetella LPS of the invention is obtainable by introducing in a Bordetella cell the expression of a heterologous acyl transferase. In particular, the modified Bordetella cell of the invention has an increased expression of an heterologous LpxA, LpxL or LpxD acyl transferase.

Abstract: The present invention relates to neisserial LPS having a hexa-acylated lipid A moiety, wherein the hexa-acylated lipid A moiety is modified as compared to the lipid A moiety of a wild-type neisserial LPS in that it comprises a palmitoleoyl instead of a lauroyl secondary acyl chain on the glucosamine at the non-reducing end of the lipid A moiety. The invention further relates to mixtures of the hexa-acylated LPS with the corresponding penta-acylated LPS, lacking a secondary acyl chain on the glucosamine at the non-reducing end of the lipid A moiety. The invention also relates to neisserial bacteria that have been genetically modified to reduce expression of the endogenous lpxL1 gene and to introduce expression of a heterologous thermosensitive lpxP gene for producing the hexa- and penta-acylated LPS.

Abstract: The present invention relates to vaccine compositions based on Gram-negative outer membrane vesicles displaying antigens of pathogens expressed as part of a fusion protein comprising N-terminal parts of surface expressed lipoproteins of Gram-negative bacteria, and use of such compositions in vaccination. The invention further relates to the fusion lipoproteins comprising N-terminal parts of surface expressed lipoproteins of Gram-negative bacteria and antigens of pathogens fused thereto, DNA constructs and bacterial host cells for expressing these fusion lipoproteins and to methods for producing outer membrane vesicles displaying the fusion lipoproteins.

Abstract: The invention relates to an improved vaccine against pertussis wherein mutants of Bordetella pertussis having a modified LPS molecule or the obtainable LPS molecules are used. These mutants or the obtainable LPS molecules may further be used as an adjuvant.

Abstract: The current invention provides new Gram negative polypeptides exhibiting lipid A 3-O-deacylase activity and are capable of modifying and/or detoxifying gram negative LPS. The present invention also provides Gram negative bacteria, Gram negative bacterial lipopolysaccharides (LPS) and compositions comprising LPS, which are provided with or treated with a 3-O-deacylase activity according to the invention and which may be used for pharmaceutical and/or veterinary purposes, in particular for the preparation of whole cell or acellular vaccines against pathogenic Gram negatives such as Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica.

Abstract: The invention relates to an improved vaccine against pertussis wherein mutants of Bordetella pertussis having a modified LPS molecule or the obtainable LPS molecules are used. These mutants or the obtainable LPS molecules may further be used as an adjuvant.

Abstract: The present invention relates to mycobacterial lipoarabinomannan cap-specific mannosyl transferases and nucleic acid encoding such transferases. The invention further relates to Mycobacteria in which the lipoarabinomannan cap-specific mannosyl transferases have been inactivated and that therefore express mannose cap-deficient lipoarabinomannan. Such Mycobacteria with mannose cap-deficient lipoarabinomannan may be used as more effective vaccines against mycobacterial diseases as they lack the immunosuppressive action of the mannose cap.

Abstract: The current invention provides new Gram negative polypeptides exhibiting lipid A 3-O-deacylase activity and are capable of modifying and/or detoxifying gram negative LPS. The present invention also provides Gram negative bacteria, Gram negative bacterial lipopolysaccharides (LPS) and compositions comprising LPS, which are provided with or treated with a 3-O-deacylase activity according to the invention and which may be used for pharmaceutical and/or veterinary purposes, in particular for the preparation of whole cell or acellular vaccines against pathogenic Gram negatives such as Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica.

Abstract: The present invention relates to Neisserial Lipo-Oligo-Saccharides (LOS) that comprise a tri-saccharide outer core that shows increased binding to the DC-SIGN receptor on dendritic cells, as a result of which the Neisserial LOS's of the invention have increased immunostimulatory activity. The tri-saccharide outer core of the Neiserial LOS's combined with a Lipid A moiety with reduced toxicity is useful as an adjuvant in vaccine preparations.

Abstract: It is possible to inactivate the early stage of lipid A synthesis of mucosal gram negative bacteria without compromising cell viability. In particular the lpxA gene in N. meningitidis was mutated and resulting lpxA knockout mutants were found to be completely lipopolysaccharide (LPS)-deficient. The major outer membrane proteins (OMPs) were detected in normal amounts. The finding provides important implications for understanding of structure and biogenesis of the outer membrane. On a practical level, the availability of LPS-deficient mutants of pathogenic mucosal bacteria such as N. meningitidis opens up new avenues to vaccine development. It enables easy isolation of endotoxin-free purified proteins, outer membranes or even whole-cell preparations for use in immunisation.

Abstract: The subject invention lies in the field of vaccines. Specifically new compounds that can be used as adjuvants are provided. Recombinant LPS having a reduced number of secondary acyl chains per molecule of LPS vis a vis the corresponding non modified LPS molecule, said secondary acyl chains being bound to primary acyl chains, said primary acyl chains being bound to the glucosamine of said recombinant LPS molecule, said recombinant LPS being homogenous in acylation pattern is an example of such a compound. Also recombinant LPS having a phosphate group attached to the glucosamine at the non reducing end of the LPS molecule and a phosphate group attached to the glucosamine at the reducing end of the molecule per recombinant LPS molecule provides a further example.