Carrier-bound immunogenic determinants and carrier therefor
First Claim
1. A carrier substance for immunogenic determinants, comprising immunogenicity-increasing carrier particles derived from gram-negative bacterial cells substantially devoid or depleted of natural immunogenic determinants of the cells and comprising that region of the cells which includes lipid A and from there ranges inwardly towards the cell interior and including cell wall material, the particles having been chemically treated with a linking reagent in an amount to provide covalently bonded intermediate linking moieties exposed on the particles, providing reactive functional groups adapted to be bonded covalently to an immunogenically effective amount of selected haptens or immunogens comprising immunogenic determinants, while preserving the adjuvant character of the lipid A and cell wall material.
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Accused Products
Abstract
An immunogenicity increasing carrier substance for immunogenic determinants is composed of particles derived from gram-negative cells substantially devoid or depleted of their natural immunogenic determinants, more particularly prepared by stripping the O-antigen and core region off the lipid A by chemical cleavage (acid hydrolysis). These socalled "naked bacteria" are chemically treated with a linking reagent to provide covalently bonded intermediate linking moieties while preserving the adjuvant effect of the particles. The linking moieties have functional groups. These serve for the covalent bonding of selected haptens or antigens comprising the desired immunogenic determinants against which antibodies are to be elicited in living antibody-producing cells. Such carrier-bound immunogenic substance can be prepared in injectable form for immunizing fowls or mammals to induce protective immunization, or to produce specific antisera or to produce antibody preparations for diagnostic, forensic, pharmacokinetic and other tests.
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Citations
43 Claims
- 1. A carrier substance for immunogenic determinants, comprising immunogenicity-increasing carrier particles derived from gram-negative bacterial cells substantially devoid or depleted of natural immunogenic determinants of the cells and comprising that region of the cells which includes lipid A and from there ranges inwardly towards the cell interior and including cell wall material, the particles having been chemically treated with a linking reagent in an amount to provide covalently bonded intermediate linking moieties exposed on the particles, providing reactive functional groups adapted to be bonded covalently to an immunogenically effective amount of selected haptens or immunogens comprising immunogenic determinants, while preserving the adjuvant character of the lipid A and cell wall material.
- 19. An immunogenic substance with inherent adjuvant properties, comprising carrier particles having an exterior surface, derived from gram-negative bacterial cells having a membrane including an outer periphery known as the cell wall and lipid A, which particles include the cell region ranging inwardly from lipid A to the membrane, both inclusive and from which particles any cell material beyond lipid A, including O-antigen has been removed by chemical cleavage whollyor predominantly and further comprising an immunogenic determinant for producing a desired immunogenic response in living, antibody-producing cells, the determinant being coalently bonded by a synthetic linking reaction to the exterior surface of the carrier particles in a form permitting immuno-recognition by antibody-producing cells, the immunogenic determinant containing immunogenic information which elicits a desired response and the adjuvant character of the particles being preserved.
- 40. In a method of raising antibodies against an immunogenic determinant which comprises challenging antibody-producing living cells with an immunogenic determinant, the improvement which comprises so challenging the cells with an immunogenic substance with inherent adjuvant properties, comprising immunogenicity-increasing carrier particles having an exterior surface, derived from gram-negative bacterial cells having a membrane including an outer periphery known as the cell wall and lipid A, which particles include the cell region ranging inwardly from lipid A to the membrane, both inclusive and from which particles any cell material beyond lipid A, including O-antigen has been removed by chemical cleavage wholly or predominantly and further comprising an immunogenic determinant for producing a desired immunogenic response in living, antibody-producing cells, the determinant being covalently bonded by a synthetic linking reaction to the exterior surface of the carrier particles in a form permitting immuno recognition by antibody-producing cells, the immunogenic determinant containing immunogenic information which elicits a desired response.
Specification