Drug – bio-affecting and body treating compositions – Lymphokine
Patent
1987-06-01
1993-10-19
Rosen, Sam
Drug, bio-affecting and body treating compositions
Lymphokine
424 89, 424 90, 424 91, 424 92, 514 2, 514 8, A61K 3900, A61K 3939
Patent
active
052543390
DESCRIPTION:
BRIEF SUMMARY
This invention relates to a new process for preparing an immunogenic complex so-called iscom.
It is known that killed viruses for example influenza virus, have a good antigenic effect. They are, however, pyrogenic even after extensive purification. By isolation of components which are important for induction of protective immunity, the pyrogenic effect has been avoided, but the immunogenicity is often not sufficiently strong. Therefore suitable adjuvants must be introduced in those vaccines containing the isolated antigens (subunits) in order to increase the immune response. On the other hand, effective adjuvants cause, in the manner in which they have been used up to now, negative side effects. Adjuvantcontaining vaccines are thus no better than vaccines based on the entire virus, as regards the pyrogenic effect.
In order to increase the immunogenicity, detergent membrane proteins have been produced, which have been entrapped or bound to the surface of liposomes (EPC Application 7940083.0). Detergent-free membrane proteins in liposomes are described in U.S. Pat. No. 4,148,876. Incorporation of adjuvants in such detergent-free unilamellar liposome products is mentioned in U.S. Pat. No. 4,196,191 (without reporting on the effect thereof). U.S. Pat. No. 4,117,113 describes negatively charged liposomes containing virus antigen. In such liposomes containing influenza haemaglutinin and neuraminidase, incorporation in liposomes of an adjuvant, mycobacterial cell walls, produces a better immune response. Better immune responses have also been obtained when adjuvants such as killed Mycobacterium tuberculosis, Bordetella pertussis and saponins have been introduced in such negatively charged liposomes containing diphtheria toxoid (U.S. Pat. No. 4,053,585). All of the above-mentioned lipid-containing membrane protein products are, however, unstable after long storage, freeze-drying or uncareful handling, e.g. high temperature.
Detergent-free and lipid-free protein micelles have also been produced as vaccine. It has been demonstrated that micelles of membrane proteins of Semliki Forest Virus (SFV) stimulate the formation of circulating antibodies against SFC and produce a protection in mice against fatal infection by SFV. On the other hand, such membrane protein micelles of parainfluenza-3-virus were not effective for stimulating antibody formation in lambs or protecting them against a dose of a PI-3-virus causing pneumonia, unless an oil adjuvant was mixed with the micelles. Oil adjuvants usually produce side effects in the form of local reactions at the infection site (EPC Application 81102213-6).
In EPC-patent application 0 109 942 there is described an immunogenic protein or peptide complex containing glycosides and a process for preparing the same. According to the process one can start from whole viruses, mycoplasmas, bacterias, parasites, animal cells but also from purified peptides or proteins or from proteins or peptides synthesized or produced by hybrid DNA technique.
These complexes have another morphological structure under electron microscopy than corresponding protein micelles produced without the addition of glycosides. The micelles have a compact central core with radially arranged spikes, while the complex according to EPC 0 109 942 has an open spherical structure consisting of circular subunits or parts of the spheric structure. The morphology is also different from that of liposomes. The complexes and the parts thereof also usually have a lower sedimentation constant than corresponding micelles and a higher sedimentation constant than the corresponding monomeric form of protein or peptide, and higher sedimentation constant than liposomes.
The complexes according to EPC 0 109 942 which have been produced with the addition of glycosides, have better immunogenic activity than corresponding protein micelles produced without the addition of glycoside or complex between a protein molecule and solubilizing agent (monomeric forms) or protein molecules bound to lipid vesicles, i.e. virosomes and produce fewe
REFERENCES:
patent: 4053585 (1977-10-01), Allison et al.
patent: 4157390 (1979-06-01), Parry et al.
patent: 4196191 (1980-04-01), Almeida et al.
patent: 4201767 (1980-05-01), Fullerton et al.
patent: 4356169 (1982-10-01), Simons et al.
patent: 4459286 (1984-07-01), Hilleman et al.
patent: 4578269 (1986-03-01), Morein
patent: 4806350 (1989-02-01), Gerber et al.
patent: 4900549 (1990-02-01), DeVries et al.
"Protein Micelles and Virosomes From the Surface Glycoproteins of Parainfluenza 3 Virus", Chemical Abstracts, vol. 96, No. 21, May 24, 1982, Abstract No. 176474d, By B. Morein et al., p. 285.
"Iscom, A Novel Structure for Antigenic Presentation of Membrane Proteins From Enveloped Viruses", Nature, vol. 308, No. 29, Mar. 1984, By B. Morein et al., pp. 457-459.
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