United States Patent:  6,080,725

Assignee:  Galenica Pharmaceuticals, Inc. (Frederick, MD)

Filed:  April 13, 1999

The present invention is directed to vaccines comprising (1) one or more bacterial, viral or tumor-associated antigens; and (2) one or more saponin-lipophile conjugate in which a lipophilic moiety such as a lipid, fatty acid, polyethylene glycol or terpene is covalently attached to a non-acylated or desacylated triterpene saponin via a carboxyl group present on the 3-O-glucuronic acid of the triterpene saponin. The attachment of a lipophile moiety to the 3-O-glucuronic acid of a saponin such as Quillaja desacylsaponin, lucyoside P, or saponin from Gypsophila, Saponaria and Acanthophyllum enhances their adjuvant effects on humoral and cell mediated immunity. Additionally, the attachment of a lipophile moiety to the 3-O-glucuronic acid residue of non- or des-acylsaponin yields a saponin analog that is easier to purify, less toxic, chemically more stable, and possesses equal or better adjuvant properties than the original saponin.

SUMMARY OF THE INVENTION

The present invention is directed to vaccine compositions comprising:

(a) one or more bacterial, viral or tumor--associated antigens, and

(b) a saponin-lipophile conjugate, in which

(1) a non-acylated or deacylated triterpene saponin having a 3-O-glucuronic acid residue is covalently attached, either directly or via a linking moiety, to:

(2) a compound having a lipophilic domain, such as a fatty acid, fatty amine, phospholipid, terpene, polyethylene glycol, among others;

wherein (1) is attached to (2) via the carboxyl carbon atom present on the 3-O-glucuronic acid residue of the triterpene saponin.

Useful antigens are peptide, polypeptide, oligosaccharide or ganglioside antigens associated with a pathogen such as a bacterium or virus that causes illness in a human or animal; or antigens associated with the presence of cancer in a human or animal.

The present invention is also directed to a method of vaccination, comprising administering a vaccine composition of the present invention.

The present invention is also directed to a method of potentiating an immune response to an antigen, comprising administering a vaccine of the present invention to an animal in need thereof.

The present invention is also directed to pharmaceutical and veterinary compositions comprising one or more of the saponin-lipophile conjugates, and one or more pharmaceutically acceptable diluents, carriers or excipients. These compositions may be employed as immunopotentiators in animals and humans.

Claim 1 of 37 Claims

1. A vaccine for human or veterinary use, comprising: (a) one or more bacterial, viral, protozoal or tumor associated antigens, and

(b) one or more saponin-lipophile conjugates, in which

(1) a non-acylated or deacylated triterpene saponin having a 3-O-glucuronic acid residue is covalently attached, either directly or via a linking moiety, to:

(2) a compound having a lipophilic domain,

wherein (1) is attached to (2) via the carboxyl carbon atom present on the 3-O-glucuronic acid residue of the triterpene saponin.

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