Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector
Patent
1998-09-25
2000-12-26
Bui, Phuong T.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
4241931, 4241941, 42419711, 4242031, 4242341, 4242581, 4242791, A61K 3900, A61K 3938, A61K 39385, A61K 39116, A61K 3902
Patent
active
06165468&
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND
Most virulent bacteria have carbohydrates on their surface, such as lipopolysaccharides and capsular polysaccharides. Antibodies directed against capsular polysaccharides provide, among other things, enhanced phagocytosis and killing of bacterial cells. Usually there are a number of serotypes of a given bacterial species, for example there are more than 80 known serotypes of Streptococcus pneumoniae related to their carbohydrate capsular structures.
Bacterial polysaccharides are classical examples of antigens that are not T helper cell-dependent, and hence, if they are immunogenic at all, they mainly induce IgM class of antibodies. This is so, because only B cells respond to them, and B cells cannot mediate the memory function as opposed to the T cells, which also mediate immunological booster effects.
In immunologically immature small children, elderly and immunosuppressed persons polysaccharides are known to be poor immunogens or not at all immunogenic.
Therefore, polysaccharide antigens which are chemically conjugated to carriers comprising T cell epitopes are effective as vaccines also for the above mentioned immunologically immature children and immunosuppressed adults.
The vaccine-producing industry has long been searching for a general method of producing conjugate-type vaccines. A general and simple method to produce such vaccines would not only be more practical but would also make process and quality control easier.
DESCRIPTION OF THE INVENTION
The present invention provides a general method of producing immunogenic products comprising antigenically active carbohydrate moieties and immunologically active carriers, which products are useful as immunizing is components in conjugate-type vaccines.
More specifically the present invention provides a method of producing an immunogenic product consisting of antigenically active carbohydrate moieties (ACM) which are each covalently coupled via identical divalent bridge groups to immunologically active carriers (IAC) containing amino groups, wherein said divalent bridge group has the following structural formula ##STR2## which comprises the steps of reductive amination of antigenically active carbohydrate moieties (ACM) to introduce amino groups on said moieties (ACM--NH.sub.2), followed by thiolation of said amino groups with iminothiolane ##STR3## whereupon the so produced thiolated products are covalently coupled to immunologically active carriers (IAC) containing aminogroups activated by treatment with N-hydroxysuccinimide bromoacetate, to produce the desired immunogenic product.
Further, the present invention provides an immunogenic product consisting of antigenically active carbohydrate moieties (ACM) which each are covalently coupled via identical divalent bridge groups to immunologically active carriers (IAC) containing amino groups, wherein said divalent bridge group has the following structural formula ##STR4##
The immunogenic products of the invention is useful as an immunizing component in vaccines.
In a preferred embodiment of the invention the antgenically active carbohydrate moieties (ACM) of the immunogenic products derive from bacterial O-polysaccharides and/or capsular polysaccharides. Specific examples of such saccharides are those which derive from Salmonella serotypes BO and/or DO.
In another preferred embodiment said antigenically active carbohydrate moieties (ACM) derive from different serotypes of Streptococcus pneumoniae capsular polysaccharides.
In yet another preferred embodiment said antigenically active carbohydrate moieties (ACM) derive from Haemophilus influenzae capsular polysaccharides.
The antigenically active carbohydrate moieties (ACM) may be synthetically produced.
The immunologically active carriers (IAC) of the immunogenic product of the invention preferably derive from polypeptides.
In a preferred embodiment of the invention said polypeptide is tetanus toxoid, diphtheria toxoid, cholera subunit B or Protein D from H. influenzae.
The invention also comprises the use of an immunogenic product according
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patent: 5204098 (1993-04-01), Szu et al.
patent: 5370872 (1994-12-01), Cryz et al.
patent: 5445817 (1995-08-01), Schneerson et al.
Blair et al., Journal of Immunological Methods, 59:129-143 (1983).
Bui Phuong T.
Lee Li
LandOfFree
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