Vaccine compositions comprising L2 and/or L3 immunotype...

Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...

Reexamination Certificate

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C424S250100, C424S184100, C424S193100, C424S194100, C424S197110, C424S203100

Reexamination Certificate

active

07838014

ABSTRACT:
The present invention relates to the field of neisserial vaccine compositions, their manufacture, and the use of such compositions in medicine. More particularly it relates to processes of making novel engineered meningococcal strains which are more suitable for the production of neisserial, in particular meningococcal, outer-membrane vesicle (or bleb) vaccines. Advantageous processes and vaccine products are also described based on the use of novel LOS subunit or meningococcal outer-membrane vesicle (or bleb) vaccines which have been rendered safer and/or more effective for use in human subjects. In particular combinations of gene downregulations are described such as PorA and OpA, PorA and OpC, OpA and Opc, and PorA and OpA and OpC. Alternatively, or in addition, lgtB−is shown to be an optimal mutation for effectively and safely using L3 and/or L2 LOS inNeisseriavaccine compositions. Bleb vaccines derived from lgtB−and capsular polysaccharide deficient meningococcal mutants are further described; as are advantageous methods of making bleb preparations where LOS is to be retained as an important antigen.

REFERENCES:
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patent: WO 01/09350 (2001-02-01), None
patent: 0209643 (2002-02-01), None
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Verheul et al., “Preparation, Characterization, and Immunogenicity of Meningococcal Immunotype L2 and L3, 7, 9 Phosphoethanolamine Group-Containing Oligosaccharide-Protein Conjugates”.Infection&Immunity, 59(3): 843-851 (1991).
Gao Lihui Hu Xujing et al., “Study on the LOS Antigenicity of 2 Candidate Strains for Meningococcal Vaccine of Serogroup B”.Biosis, XP002133714 (Abstract).
Wakarchuk et al., “Functional Relationships of the Genetic Locus Encoding the Glycosyltransferase Enzymes Involved in Expression of the Lacto-N-Neotetraose Terminal Lipopolysaccharide Structure inNeisseria meningtidis”. J. Biol. Chem., 271(32): 19166-19173 (1996).
Quakyi et al., “Modulation of the Biological Activities of Meningococcal Endotoxins by Association with Outer Membrane Proteins is not Inevitably Linked to Toxicity”.Infection&Immunity, 65(5): 1972-1979 (1997).
Gu et al., “Preparation, Characterization, and Immunogenicity of Meningococcal Lipooligosaccharide-Derived Oligosaccharide-Protein Conjugates”.Infection&Immunity, 61(5): 1873-1880 (1993).
Zakirov et al., “Immunological Activity ofNeisseria meningitidisLipooligosaccharide Incorporated into Liposomes”.Zhurnal Mikrobiologii Epidemiologii I Immunobiologii, 0(1): 49-53 (1995).
Van Der Voort et al.; “Specificity of Human Bactericidal Antibodies against PorA P1.7,16 Induced with a Hexavalent Meningococcal Outer Membrance Vesicle Vaccine”; Infection and Immunity; 1996; vol. 64, No. 7; pp. 2745-2751.

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