De Staat Der Nederlanden Vertegenwoordigd Door De Minister Van Welzijn, Volksgezondheid En Cultuur

De Staat Der Nederlanden, Vertenwoordigd Door De Minister Van Welzijn, Volksgezondheil En Cultuur

Liana Juliana Josephine Margriet Steeghs

Peter André Van Der Ley

Peter Andre Van Der Ley

Hendrik Jan Hamstra

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 inwas 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 asopens 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.

Mutants of gram negative mucosal bacteria and application thereof in vaccines

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.

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Utrecht, Netherlands

Liana Juliana Josephine Margriet Steeghs