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 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 is related to the use of topical formulations that contain epidermal growth factor encapsulated in or associated to deformable or conventional liposomes to be applied on the surface of and around chronic ischemic skin lesions. The formulations of the present invention, in contrast with the previous art, are useful because they provide a high bioavailability of EGF in the tissue deep below the lesions and for preventing diabetic foot amputation.

Abstract: The present invention is related to the field of biotechnology and genetic engineering techniques, particularly to a method for obtaining mutants obtain from streptokinase, to the molecules obtained from this method, as well as the expression vectors and microorganisms for recombinant obtaining. The object of the present invention is to achieve streptokinase mutants from modifications of skc-2 gene coding for streptokinase SKC-2 (Heberkinase®), such that the obtained mutants conserve their capacity for plasminogen activator complex formation having reduced antigenicity, that could constitute preferred alternatives to native streptokinase for thrombolytic therapy. The molecules obtained from present invention can be used in the treatment of disorders as myocardial infarct, pulmonary thromboembolism, surgical complications and other cases of thrombosis.

Abstract: The present invention is related to the field of biotechnology and genetic engineering techniques, particularly to a method for obtaining mutants obtain from streptokinase, to the molecules obtained from this method, as well as the expression vectors and microorganisms for recombinant obtaining. The object of the present invention is to achieve streptokinase mutants from modifications of skc-2 gene coding for streptokinase SKC-2 (Heberkinase®), such that the obtained mutants conserve their capacity for plasminogen activator complex formation having reduced antigenicity, that could constitute preferred alternatives to native streptokinase for thrombolytic therapy. The molecules obtained from present invention can be used in the treatment of disorders as myocardial infarct, pulmonary thromboembolism, surgical complications and other cases of thrombosis.