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 the fields of medical microbiology and vaccines. In particular the invention relates to a process wherein the spontaneous release of bacterial outer membrane vesicles (OMV) of Gram-negative bacteria is stimulated by application of a dissolved oxygen tension (DOT) that is higher than a physiological DOT. The thus produced OMVs are for use in vaccines. The invention further relates to OMV obtainable by said process, and to a pharmaceutical composition comprising such OMV. The present invention further relates to the use of OMV of the present invention as a medicament in particular for use in a method for eliciting an immune response.

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 pneumoviral virions comprising a viral genome that has a mutation in a gene coding for a protein that is essential for infectivity of the pneumovirus, whereby the mutation causes a virus produced from only the viral genome to lack infectivity, and whereby the virion comprises the protein in a form and in an amount that is required for infectivity of the virion. The invention also relates to methods for producing the pneumoviral virions and for using the virions in the treatment or prevention of pneumoviral infection and disease. A preferred pneumoviral virion is a virion of Respiratory Syncytial Virus in which preferably the gene for the G attachment protein is inactivated and complemented in trans.

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 methods for producing dried formulations of biopharmaceutical agents that aim to minimize the loss of activity of the agents upon drying and to provide dried formulations with an extended shelf life. The method comprises the step of drying an aqueous solution comprising, in addition to the biopharmaceutical agent, at least an amino acid, a polyol and a metal salt. Preferably the amino acid is glutamate, the polyol is sorbitol and optionally also mannitol and the metal salt is a magnesium salt. The solution is dried by vacuum drying or by lyophilization. The methods are particularly useful for preparing dried formulations of viruses such as poliovirus or respiratory syncytial virus to be used for vaccination. The invention also relates to dried formulations prepared in accordance with the methods of the invention and to their use as medicaments, e.g. as vaccines.

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 a method for prevention and/or reduction of aggregation of viral components.

Abstract: The invention relates to pneumoviral virions comprising a viral genome that has a mutation in a gene coding for a protein that is essential for infectivity of the pneumovirus, whereby the mutation causes a virus produced from only the viral genome to lack infectivity, and whereby the virion comprises the protein in a form and in an amount that is required for infectivity of the virion. The invention also relates to methods for producing the pneumoviral virions and for using the virions in the treatment or prevention of pneumoviral infection and disease. A preferred pneumoviral virion is a virion of Respiratory Syncytial Virus in which preferably the gene for the G attachment protein is inactivated and complemented in trans.

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 methods for producing dried formulations of biopharmaceutical agents that aim to minimize the loss of activity of the agents upon drying and to provide dried formulations with an extended shelf life. The method comprises the step of drying an aqueous solution comprising, in addition to the biopharmaceutical agent, at least an amino acid, a polyol and a metal salt. Preferably the amino acid is glutamate, the polyol is sorbitol and optionally also mannitol and the metal salt is a magnesium salt. The solution is dried by vacuum drying or by lyophilization. The methods are particularly useful for preparing dried formulations of viruses such as poliovirus or respiratory syncytial virus to be used for vaccination. The invention also relates to dried formulations prepared in accordance with the methods of the invention and to their use as medicaments, e.g. as vaccines.

Abstract: The invention relates to pneumoviral virions comprising a viral genome that has a mutation in a gene coding for a protein that is essential for infectivity of the pneumovirus, whereby the mutation causes a virus produced from only the viral genome to lack infectivity, and whereby the virion comprises the protein in a form and in an amount that is required for infectivity of the virion. The invention also relates to methods for producing the pneumoviral virions and for using the virions in the treatment or prevention of pneumoviral infection and disease. A preferred pneumoviral virion is a virion of Respiratory Syncytial Virus in which preferably the gene for the G attachment protein is inactivated and complemented in trans.

Abstract: The present invention relates to methods for producing dried formulations of biopharmaceutical agents that aim to minimize the loss of activity of the agents upon drying and to provide dried formulations with an extended shelf life. The method comprises the step of drying an aqueous solution comprising, in addition to the biopharmaceutical agent, at least an amino acid, a polyol and a metal salt. Preferably the amino acid is glutamate, the polyol is sorbitol and optionally also mannitol and the metal salt is a magnesium salt. The solution is dried by vacuum drying or by lyophilization. The methods are particularly useful for preparing dried formulations of viruses such as poliovirus or respiratory syncytial virus to be used for vaccination. The invention also relates to dried formulations prepared in accordance with the methods of the invention and to their use as medicaments, e.g. as vaccines.

Abstract: The present invention relates to the fields of medical microbiology and vaccines. In particular the invention relates to a process for detergent-free preparation of outer membrane vesicles (OMV) of Gram negative bacteria for use in vaccines, to OMV obtainable by said process, and to a pharmaceutical composition comprising such OMV. The present invention further relates to the use of OMV of the present invention as a medicament in particular for use in a method for eliciting an immune response.

Abstract: The present invention relates to a method for prevention and/or reduction of aggregation of viral components.

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 the fields of medical microbiology and vaccines. In particular the invention relates to a process for detergent-free preparation of outer membrane vesicles (OMV) of Gram negative bacteria for use in vaccines, to OMV obtainable by said process, and to a pharmaceutical composition comprising such OMV. The present invention further relates to the use of OMV of the present invention as a medicament in particular for use in a method for eliciting an immune response.

Abstract: The invention relates to pneumoviral virions comprising a viral genome that has a mutation in a gene coding for a protein that is essential for infectivity of the pneumovirus, whereby the mutation causes a virus produced from only the viral genome to lack infectivity, and whereby the virion comprises the protein in a form and in an amount that is required for infectivity of the virion. The invention also relates to methods for producing the pneumoviral virions and for using the virions in the treatment or prevention of pneumoviral infection and disease. A preferred pneumoviral virion is a virion of Respiratory Syncytial Virus in which preferably the gene for the G attachment protein is inactivated and complemented in trans.

Abstract: The invention relates to pneumoviral virions comprising a viral genome that has a mutation in a gene coding for a protein that is essential for infectivity of the pneumovirus, whereby the mutation causes a virus produced from only the viral genome to lack infectivity, and whereby the virion comprises the protein in a form and in an amount that is required for infectivity of the virion. The invention also relates to methods for producing the pneumoviral virions and for using the virions in the treatment or prevention of pneumoviral infection and disease. A preferred pneumoviral virion is a virion of Respiratory Syncytial Virus in which preferably the gene for the G attachment protein is inactivated and complemented in trans.