Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...
Patent
1995-05-01
1998-01-06
Housel, James C.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Bacterium or component thereof or substance produced by said...
4242821, 5361231, 435 72, 4351721, A61K 39095, A61K 4500, C07H 100, C12N 1500
Patent
active
057051615
DESCRIPTION:
BRIEF SUMMARY
The subject invention is directed at an immunity providing B cell activating molecule derived from a meningococcal lipopolysaccharide (LPS), said molecule comprising at least one epitope, said molecule comprising at least the common portion of the oligosaccharide portion (core region) of lipopolysaccharides which are specific for at least two meningococcal immunotypes. The invention is also directed at methods for the preparation thereof, both synthetically and through recombinant-DNA-techniques. Furthermore, the subject invention is directed at an outer membrane vesicle provided with a group of polypeptides which possess at least the immuo activity of outer membrane proteins (OMP's) bound to a membrane. The invention is also directed at a vaccine comprising such a molecule and/or such an outer membrane vesicle. A method for preparing such an outer membrane vesicle also falls within the scope of protection of the subject invention.
It is known that vaccines of purified capsular polysaccharides (CPS) can induce protective immunity. This immunity depends on the age of the vaccinated person and is only of a short duration. The intrinsic disadvantages of capsular polysaccharides as vaccines are circumvented by the classic approach of coupling capsular polysaccharides or oligosaccharides to be derived therefrom with proteins (Goebel, W. F., and O. T. Avery 1929 J. Exp. Med. 50:533-550 and Cruse, J. M. and R. E. Lewis (Ed.) 1989 Contrib. Microbiol. Immunol. Basel. Krager, 10:1-196). The coupling of polysaccharides to proteins results in changing the character of this type of antigen from thymus independent to thymus dependent. Such poly or oligosaccharide protein conjugates are in general very immunogenic in young children and can induce memory.
A number of examples of known saccharide peptide conjugates follow:
Conjugates of capsular polysaccharides (CPS) of H. influenza b with tetanus toxoid (TT) are known from the Dutch Patent Application 8602325.
Conjugates of capsular polysaccharides of meningococcal group A and C with tetanus toxoid were prepared, said conjugates appear to be very A. B. Leussink, 1983. Physicochemical and immunological characterization of meningococcal group A and C polysaccharide-tetanus toxoid conjugates van Delft and K. Haverkamp, 1983. Preparation and immunochemical characterization of meningococcal group C polysaccharide tetanus toxoid conjugates as a new generation of vaccines. Infect. Immun. 40:39-45! and and C meningococcal polysaccharide-tetanus toxoid conjugates. J. Immunol. 127:1011-1018!).
Group B Meningococcus a bacteria group causing more than 50% of the cases of meningococcal disease in many countries is a group of bacteria whose capsular polysaccharides do not induce immune reaction or induce little immune reaction. (Poolman et al., The Lancet, September 1986, pages 555-558).
Therefore, a search has been carried out for the group B Meningococcus for the saccharide peptide conjugates that could be useful in a vaccine as capsular polysaccharides of this group do not give any immune reaction against gramnegative bacteria in test animals and human volunteers. Therefore, saccharide peptide conjugates were made with modified capsular Gamian, 1986. Induction of meningococcal group B polysaccharide-specific IgG antibodies in mice using an N-proprionylated B polysaccharide tetanus 1989. The capsular polysaccharide of group B Neisseria meningitidis as a vehicle for vaccine development. In Cruse, J. M., and R. E. Lewis, Conjugate Vaccines. Contrib. Microbiol. Immunol. Basel, Krager, 10:151-165!).
As it is suspected that anti group B antibodies (in particular IgG) demonstrate in vivo cross reaction with host antigens and as the use of a saccharide peptide conjugate comprising modified capsular polysaccharide of group B Meningococcus could therefore lead to causing auto immune disease most research is directed at a vaccine against group B Meningococcus is directed at the potential use of sub capsular components such as outer membrane proteins (OMP) and lipopolysaccharides (LPS).
So Jenn
REFERENCES:
E. Wiertz et al., "T Cell Recognition of Neisseria meningitidis Class 1 Outer Membrane Proteins", The Journal of Immunology, Sep. 15, 1991, vol. 147, No. 6, pp. 2012-2018.
A. Verheul et al., "Minimal Oligosaccharide Structures Required for Induction of Immune Responses against Meningococcal Immunotype L1, L2, and L3, 7, 9 Lipopolysaccharides Determined by Using Synthetic Oligosaccharide-Protein Conjugates", Infection and Immunity, Oct. 1991, vol. 59, No. 10, pp. 3566-3573.
A. Verheul et al., "Preparation, Characterization, and Immunogenicity of meningococcal Immunotype L2 and L3, 7, 9 Phosphoethanolamine Group-Containing Oligosaccharide-Protein Conjugates", Infection and Immunity, Mar. 1991, vol. 59, No. 3, pp. 843-851.
M. Frosch et al., "Molecular characterization and expression in Escherichia coli of the gene complex encoding the polysaccharide capsule of Neissaria meningitidis group B", Microbiology, Mar. 1989, vol. 86, pp. 1669-1673.
G. Boons et al., "Preparation of a Well-Defined Sugar-Peptide Conjugate: A Possible Approach to a Synthetic Vaccine Against Neisseria meningitidis", pp. 303-308.
C. Frasch, "Vaccines for Prevention of Meningococcal Disease", Clinical Microbiology Reviews, Apr. 1989, vol. 2, pp. S134-S138.
Verheul et al, Micro. Rev., Mar. 1993, 57(1):34-49.
Robertson et al., Molec. Microbio, 1993, 8(5):891-901.
Hoogerhout Peter
Poolman Jan Theunis
Van Der Ley Peter Andre
De Staat der Nederlanden, Vertegenwoordigd Door de Minister Van
Housel James C.
Shaver Jennifer
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