Proteinaceous adjuvants

Abstract

A modulated immune response to an antigen is achieved by coadministering the antigen and a genetically-detoxified pertussis holotoxin, particularly one retaining its immunogenicity, to a host. The modulated immune response enables immunogenic compositions, including multivalent pediatric vaccines, such as DTP, to be provided which produce a modulated immune response in the absence of extrinsic adjuvants, such as alum. The adjuvanting effect achieved by the genetically-detoxified pertussis holotoxin enables at least the same level of adjuvanting effect to be achieved as previously attained by alum, without the undesirable side effects thereof.

Description

REFERENCE TO RELATED APPLICATION[0001] This application is a continuation-in-part of copending U.S. patent application Ser. No. 08 / 258,228 filed Jun. 10, 1994.[0002] The present invention relates to the field of immunology and is particularly concerned with proteinaceous adjuvants., i.e. materials which modulate immune responses to an antigen.[0003] Vaccines have been used for many years to protect humans and animals against a wide variety of infectious diseases. Such conventional vaccines consist of attenuated pathogens (for example, polio virus), killed pathogens (for example, Bordetalla pertussis) or immunogenic components of the pathogen (for example, diphtheria toxoid). Some antigens are highly immunogenic and are capable alone of eliciting immune responses. Other antigens, however, fail to induce, for example, a protective immune response or induce only a weak immune response.[0004] Immunogenicity can be significantly improved if the antigens are co-administered with adjuvants...

AI Technical Summary

Benefits of technology

[0026] However, the genetically-detoxified pertussis holotoxin surprisingly provides a modulation of the immune response of a non-Bordetella antigen which enables vaccine formulations and other immunogenic compositions to be provided which exhibit immune responses at least equivalent to those achieved by adjuvanting with alum.

Problems solved by technology

Other antigens, however, fail to induce, for example, a protective immune response or induce only a weak immune response.

Some of these adjuvants are toxic, however, and can cause undesirable side-effects, making them unsuitable for use in humans and many animals Indeed, only aluminum hydroxide and aluminum phosphate (collectively commonly referred to as alum) are routinely used as adjuvants in human and veterinary vaccines.

While the usefulness of alum is well established for some applications, it has limitations.

For example, it is ineffective for influenza vaccination and inconsistently elicits a cell mediated immune response.

The antibodies elicited by alum-adjuvanted antigens are mainly of the IgG1 isotype in the mouse, which may not be optimal for protection by some vaccinal agents.

Although the whole cell pertussis vaccine is effective in preventing the incidence and spread of disease, the acceptance and uptake of the vaccine has been limited due to reports of vaccine associated adverse effects.

Although the acellular vaccine has been demonstrated to be immunogenic and of comparable efficacy to the whole cell vaccine, it has not been as effective in preventing bacterial colonization (ref.

Although the preceeding formulations demonstrate the advantages of improved safety and efficacy associated with the use of a genetically detoxified pertussis toxin molecule, they do not address the adverse effects of DPT (diphtheria, pertussis and tetanus) vaccination not associated with the pertussis molecule component (refs.

Elimination of alum, therefore, would be expected to lead to a less effective formulation and would be unlikely to have been proposed.

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