Drug – bio-affecting and body treating compositions – Lymphokine
Patent
1980-11-17
1983-08-23
Fagelson, Anna P.
Drug, bio-affecting and body treating compositions
Lymphokine
260112R, 424 85, 424 86, 424 87, 424 89, 424 91, 424 92, 436543, A61K 3900, A61K 39385, C07G 700
Patent
active
044003765
DESCRIPTION:
BRIEF SUMMARY
This invention relates to immunological preparations, particularly those containing antigenic materials.
Immunisation, for example against infectious diseases, is widely used in both a human and a veterinary context. It is often the case, however, that the antigenic material contained in the immunological preparation is not as immunogenic as could be desired, necessitating the use of a plurality of injections of the preparation. As an alternative, or in addition to the use of repeated injections, an adjuvant may be incorporated in the immunological preparation in order to increase the immune response provoked by the antigenic material. However, the effective adjuvants at present available, for example Freund's incomplete and complete adjuvants, have disadvantages particularly for human use. For some time, therefore, attempts have been made to discover new forms of adjuvant which would simplify immunization procedures and reduce the amounts of antigenic material required or amplify the response to a given quantity of antigenic material. Such an effect is applicable not only for protective immunization but also for the production of therapeutic or diagnostic immunological and serological reagents.
In U.K. Pat. Application No. 7838177 there is described and claimed a novel form of immunologically active preparation based upon the discovery that members of a group of naturally occurring substances have the effect of increasing the immunogenicity of antigenic materials when administered in combination therewith. Such preparations comprise an antigenic material in combination with an MHC (Major Histocompatibility Complex) antigen.
I have now developed a new approach to the production of such combinations of antigenic material with MHC antigen which has particular advantages as compared with the modes of preparation described in U.K. Patent Application No. 7838177.
Accordingly the present invention comprises an antigenic material in combination with an MHC antigen which is itself in the form of a complex with a protein with which it is normally associated in nature, said antigenic material being attached to the protein of the complex through antibody to that protein.
MHC antigens have been found in all animal species (including man) where they have been sought, being carried on the surface of nucleated cells of tissues, and constitute a particularly polymorphic system within any species. Therefore, although it is necessary in order for the MHC antigen to enhance the immunogenicity of the antigen material with which it is combined, that the MHC antigen should contain an antigenic determinant or determinants foreign to the recipient, the extreme polymorphism of these MHC antigens is generally sufficient to ensure that this is the case between one member of a species and another, except in the extreme case of members of a species which are genetically identical. The MHC antigen may therefore be from either the same species or another species, for example a phylogenetically similar species such as a primate in the case of preparations for human administration. MHC antigen from the same species may often be preferred, however, unless there are reasons, particularly an enhancement of effect, for using MHC antigen from another species.
One major group of MHC antigens to which the present invention is applicable comprises the HLA antigens which are found in man and the analogous antigens of other species. Such MHC antigens are referred to by many workers as SD (Serologically Determined) antigens. A second group of MHC antigens of some interest which may be distinguished from these Serologically Determined MHC antigens, are those antigens such as the Ia antigens of mice and their equivalents in man (DRW) and other animal species. Examples of the MHC antigens analogous to HLA in other species are RLA in rabbits and H-2 in mice, etc. The MHC antigens of a combination according to the present invention may be of various specificities. Moreover, they may comprise not only the whole molecule which occurs in nature but also a p
REFERENCES:
Fujimoto, J. of Immunol. vol. 111, 1973, pp. 1093-1100.
Gooding, The J. Exptl. Med., vol. 140, 1974, pp. 61-78.
Klaus, Immunology, vol. 34, 1978, pp. 643-653.
Henning, Nature, vol. 263, Oct. 21, 1976, pp. 689-691.
Garrido, Nature, vol. 261, Jun. 24, 1976, pp. 705-707.
Parham, Nature, vol. 276, Nov. 23, 1978, pp. 397-399.
Sanderson, Nature, vol. 269, Sep. 29, 1977, pp. 414-417.
Fagelson Anna P.
National Research Development Corporation
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