Vaccines

Details Vaccines Vaccines

1996-05-08

1999-03-02

Minnifield, Nita

Drug, bio-affecting and body treating compositions

Antigen, epitope, or other immunospecific immunoeffector

4242781, 424450, 4241981, 4242771, 424417, 514 2, 514955, A61K 3900, A61K 9127, A01N 2526, A01N 3718

Patent

active

058767215

DESCRIPTION:

BRIEF SUMMARY
The present invention relates to vehicles having novel compositions and to their use as an adjuvant, particularly for orally administered vaccines as well as to vaccines administered by the conventional parenteral route.
Vehicles composed of various types of amphipathic molecules are known. These include liposomes, which have a phospholipid bilayer, and non-ionic surfactant vesicles (NISV), in which the vesicles are formed essentially of non-ionic surfactants (NIS) such as polyoxyethylene aliphatic ethers. Both types of vesicle have an aqueous compartment enclosed by the bilayer or lamella within which various molecules can be entrapped as solutes.
Vesicles comprising a phospholipid bilayer occur naturally and are important in biological systems, eg. as microsomes. Non-ionic surfactant vesicles (NISV) are used in the cosmetic field e.g. as moisturising agents.
By virtue of the ability to entrap or encapsulate molecules, these vesicles are used in the medical field as carriers, e.g. for drug delivery.
As is described in our international patent application no. PCT/GB93/00716 filed 6th Apr. 1993, non-ionic surfactant vesicles containing entrapped antigens act as potent immunological adjuvants.
We have now found that a new type of vesicle structure comprising non-ionic surfactants together with molecules having the ability to transport, or facilitate the transport of, fats, fatty acids, and lipids across mucosal membranes (hereinafter termed "transport enhancers") are capable, when an antigen is entrapped therein, of acting as potent immunological adjuvants, the adjuvant effect being particularly striking with vaccines of this type administered orally.
Thus according to one aspect the present invention provides at least one antigen entrapped in vesicles comprising at least one non-ionic surfactant and at least one molecule having the ability to transport, or facilitate the transport of, fats, fatty acids and lipids across mucosal membranes.
According to a further aspect, we provide a composition comprising vesicles with entrapped antigen according to the invention together with a pharmaceutically acceptable carrier or excipient. In a preferred aspect, the composition is in a form suitable for oral administration.
Adjuvants are agents which assist in stimulating the immune response, a property which is highly desirable for certain antigens, notably those of low molecular weight such as peptides, which are inherently weak stimulators of the immune system even when coupled to carriers.
Although the use of adjuvants can overcome these problems, many adjuvants introduce further difficulties. The only adjuvant currently licensed for use in man is aluminium hydroxide. However, aluminium hydroxide is not considered to be an adequate adjuvant for all antigens as it does not adequately boost cell-mediated immunity (CMI), an essential property if a vaccine is to be successful, especially against intracellular pathogens such as Leishmania, Toxoplasma and viruses. Freund's Complete Adjuvant (FCA) does stimulate cellular immunity but is unsuitable for human or veterinary use as it promotes granuloma formation, adhesions, and other toxic side effects. FCA also produces a local inflammatory reaction which can persist for months. There is an urgent need for new non-toxic adjuvants which promote cell-mediated immunity. Indeed, such adjuvants will be essential if the full potential of vaccines based on peptide antigens is to be realised. This need is met at least to a major extent by the adjuvants of the present invention/
Thus according to another aspect, the present invention provides a vaccine comprising at least one antigen entrapped in vesicles comprising at least one non-ionic surfactant and at leas one molecule having the ability to transport, or facilitate the transport of, fats, fatty acids and lipids across mucosal membranes.
According to another aspect, the present invention provides a method of potentiating the immunological response to at least one antigen in a mammalian or non-mammalian subject which comprises adm

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