Abrégé

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.

Classes IPC  ?

• A61K 39/00 - Préparations médicinales contenant des antigènes ou des anticorps
• A61K 39/02 - Antigènes bactériens
• A61K 35/74 - Bactéries
• C07K 14/47 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'animauxPeptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant d'humains provenant de vertébrés provenant de mammifères

Abrégé

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.

Classes IPC  ?

• C12N 1/20 - BactériesLeurs milieux de culture
• C12P 1/04 - Préparation de composés ou de compositions, non prévue dans les groupes , utilisant des micro-organismes ou des enzymesProcédés généraux de préparation de composés ou de compositions utilisant des micro-organismes ou des enzymes utilisant des bactéries
• C12P 21/02 - Préparation de peptides ou de protéines comportant une séquence connue de plusieurs amino-acides, p. ex. glutathion
• A61K 39/095 - Neisseria
• A61K 39/02 - Antigènes bactériens
• A61K 39/108 - EscherichiaKlebsiella

Abrégé

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 Bordetellacell 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.

Classes IPC  ?

• C07K 14/235 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant de bactéries provenant de Bordetella (G)
• A61K 39/02 - Antigènes bactériens
• C12N 9/10 - Transférases (2.)

Abrégé

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 lpxL1or 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.

Classes IPC  ?

• C07H 15/06 - Radicaux acycliques non substitués par des structures cycliques liés à un atome d'oxygène d'un radical saccharide le radical acyclique étant un groupe hydroxyalkyle estérifié par un acide gras
• A61K 31/7024 - Esters de saccharides
• A61K 31/715 - Polysaccharides, c.-à-d. ayant plus de cinq radicaux saccharide liés les uns aux autres par des liaisons glycosidiquesLeurs dérivés, p. ex. éthers, esters
• A61P 31/04 - Agents antibactériens

Abrégé

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 lpxL1geneand to introduce expression of a heterologous thermosensitive lpxP gene for producing the hexa-and penta-acylated LPS. By selecting the time and/or temperature at which the bacterium is grown, it is feasible to increase or decrease the amount of hexa-acylated lipid A structure relative to the corresponding penta-acylated structure and thereby modulate the TLR4 agonist activity of the neisserial LPS of the invention,to the exact level of activity required for a particular immunotherapeutic approach.

Classes IPC  ?

• C07H 15/06 - Radicaux acycliques non substitués par des structures cycliques liés à un atome d'oxygène d'un radical saccharide le radical acyclique étant un groupe hydroxyalkyle estérifié par un acide gras
• A61K 31/7024 - Esters de saccharides
• A61P 31/04 - Agents antibactériens

Abrégé

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.

Classes IPC  ?

• A61K 35/744 - Bactéries lactiques, p. ex. entérocoques, pédiocoques, lactocoques, streptocoques ou leuconostoques
• C07K 14/195 - Peptides ayant plus de 20 amino-acidesGastrinesSomatostatinesMélanotropinesLeurs dérivés provenant de bactéries
• C12N 15/62 - Séquences d'ADN codant pour des protéines de fusion

Abrégé

The present invention relates to a method forprevention and/or reduction of aggregation of viral components.

Classes IPC  ?

• A61K 39/13 - Virus de la poliomyélite
• C12N 7/00 - Virus, p. ex. bactériophagesCompositions les contenantLeur préparation ou purification

Abrégé

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.

Classes IPC  ?

• A61K 9/19 - Préparations médicinales caractérisées par un aspect particulier à l'état particulaire, p. ex. poudres lyophilisées
• A61K 47/02 - Composés inorganiques
• A61K 47/18 - AminesAmidesUréesComposés d’ammonium quaternaireAcides aminésOligopeptides ayant jusqu’à cinq acides aminés
• A61K 47/26 - Hydrates de carbone, p. ex. polyols ou sucres alcoolisés, sucres aminés, acides nucléiques, mono-, di- ou oligosaccharidesLeurs dérivés, p. ex. polysorbates, esters d’acide gras de sorbitan ou glycyrrhizine

Abrégé

The present invention relates to methods for identifying and/or distinguishing polioviral strains, in particular polioviral strains used in vaccine production. The methods are based on selective hybridisation with oligonucleotides, i.e. primers and/or probes, that allow to distinguish between closely related but different polioviral strains on the basis of nucleotidepolymorphisms existing between those polioviral strains. Preferably, the methods employ amplification or amplification-ligation assays for detecting the selective hybridisation. The invention further relates to oligonucleotides for use in the methods of the invention and kits comprising such oligonucleotides and optionally enzymes and buffers for carrying out the methods of the invention. label

Classes IPC  ?

• C12Q 1/70 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des virus ou des bactériophages
• C12Q 1/68 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismesCompositions à cet effetProcédés pour préparer ces compositions faisant intervenir des acides nucléiques