Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Liposomes
Patent
1995-09-18
1998-06-02
Achutamurthy, Ponnathapura
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Liposomes
4242781, 4242791, A61K 9127, A61K 4500
Patent
active
057595720
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a method of producing a liposome preparation capable of efficiently inducing cellular immunity, and the liposome may be widely used as an adjuvant (immunostimulating aid) for vaccines and immunotherapeutic agents.
BACKGROUND ART
Because antigens in vaccines and immunotherapeutic agents generally do not elicit an effective immune response by themselves, adjuvants are used as aids to increase immunogenicity. Many substances and preparations with an adjuvant action have been reported as a result of research, but most of these have not been put into practical use due to their strong toxicity, except for aluminum phosphate adjuvants and alum adjuvants, consisting mainly of aluminum hydroxide, being suitable for use in humans.
As an alternative method, there is described in Japanese Unexamined Patent Publication No. 2-188532 a liposome vaccine prepared by reconstructing an antigen-presenting glycoprotein into a liposome. Immunity is largely classified into humoral immunity and cellular immunity, and although alum adjuvants are capable of inducing humoral immunity in a relatively efficient manner, they are not very effective at inducing cellular immunity. Yet in recent years it has gradually become clear that the role of cellular immunity is very important in treatment of persistently infectious viral diseases such as AIDS (J. Salk et al., Science 260, 1270-1271, 1993; M. Sugimoto, K. Ohishi and Y. Ikawa, Immunol. Today 14, 190-191, 1993).
Consequently, there has emerged a need to develop adjuvants capable of inducing strong cellular immunity. Liposomes coated with high-molecular polysaccharides such as mannan are reported to have strong cellular immunity-inducing properties (Y. Noguchi et al., J. Immunol., 143, 3737-3742, 1989). Also, WO92/04887 describes liposomes coated with mannose-containing polysaccharides. However, mannan is a mixture of polymannoses of differing sizes, and it is known to exhibit a strong toxicity in the body (Mikami, K. et al., Summary of 15th Carbohydrate Symposium, 43-44, 7/29/93, 30 days, Sendai), and is thus not suitable for use as a drug.
In other words, mannan, being a large polysaccharide consisting of 50 to 100 mannose residues, is also non-uniform in terms of molecular weight, and little is known about its structure, including saccharide bond forms. This polysaccharide produces antibodies when inoculated into animals (it has antigenicity), and as mentioned above it is known to be highly toxic.
DISCLOSURE OF THE INVENTION
The present invention, therefore, is aimed at providing a liposome to be used for humans, which has effective adjuvant activity to induce cellular immunity and which has low toxicity and antigenicity.
As a result of much research intended to overcome the above-mentioned problems, the present inventors have found that liposomes which have oligosaccharide on their surface which consists of 2 to 11 saccharide residues and binds to lectin of antigen presenting cells has effective adjuvant activity to induce cellular immunity and also has low toxicity and antigenicity, to allow its use for humans.
Consequently, the present invention provides liposomes which have oligosaccharide on their surface which consists of 2 to 11 saccharide residues and binds to lectin of antigen-presenting cells.
The present invention further provides a vaccine prepared by encapsulating an antigen in the above-mentioned liposomes.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a graph showing the results of Experiment I.
FIG. 2 is a graph showing the results of Experiment II.
FIG. 3 is a graph showing the results of Experiment III.
FIG. 4 is a graph showing the results of Experiment IV.
In the figures, the shaded bars indicate average arithmetic means, and the solid lines indicate standard error.
DETAILED DESCRIPTION OF THE INVENTION
The liposomes of the present invention have effective adjuvant activity to induce cellular immunity while both their toxicity and own antigenicity are considered to be low; consequently they may be used as
REFERENCES:
patent: 5169636 (1992-12-01), Nanba et al.
patent: 5686103 (1997-11-01), Redziniak et al.
Hatanaka Masakazu
Mizuochi Tsuguo
Ohishi Kazue
Sugimoto Masanobu
Achutamurthy Ponnathapura
Meller Michael N.
Tonen Corporation
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