Id Biomedical Corporation of Quebec

Other

US Government As Represented by the Secretary of the Army

The Council of the Queensland Institute of Medical Research

U.S. Army Medical Research Materiel Command

George H Lowell

David S Burt

David Hugh Jones

Clement Rioux

Joseph J Zimmermann

Gregory Lee White

Kirkor Torossian

Louis F Fries, Iii

Martin Plante

Wendell David Zollinger

James F Wood

Michael Good

George L White

Tomas B Leanderson

Michael R Batzloff

David Jones

David H Jones

Methods for making and using therapeutic formulations of Proteosome-based immunoactive compositions are provided. The immunogenic compositions, which include Proteosomes and liposaccharides, may be used to elicit or enhance a nonspecific innate immune response to, for example, treat or prevent infectious disease. In addition, after activating the innate immune system, immunogenic compositions further containing an antigen may be used to elicit a specific adaptive immune response. Furthermore, provided are compositions capable of altering hyperreactive responses or inflammatory immune responses, such as allergic reactions. Such compositions may be used as a prophylactic, or in various clinical settings to treat or prevent infectious disease (such as parasite, fungal, bacterial or viral infections), or to alter inappropriate inflammatory immune responses (such as allergic reactions or asthma).

Compositions and methods for activating innate and allergic immunity

An adjuvant complex composed of bacterial outer membrane protein proteosomes complexed to bacterial liposaccharide is prepared to contain the component parts under a variety of conditions. The complex can be formulated with antigenic material to form immunogenic compositions, vaccines and immunotherapeutics. An induced immune response includes protective antibodies and/or type 1 cytokines is shown for a variety of protocols.

Proteosome-liposaccharide vaccine adjuvant

Improved forms of vaccines which comprise proteosomes and protein antigens are described. Vaccines which contain influenza HA as the antigen are used for illustration as to demonstrate efficacy. Improvements in the preparation of the vaccines themselves and the proteosome component are also included.

Proteosome influenza vaccine

Effective stimulation of immune responses is achieved through the use of a group A streptococcal antigen combined with proteosome adjuvant. The compositions are provided in particular for intranasal administration. The vaccine compositions are provided for use in inducing an immune response in an individual for the treatment or prophylaxis of group A streptococcal infection in an individual, preferably via prevention or reduction of colonisation of the throat following intranasal administration.

Vaccine

An immunogenic complex, essentially consisting of neisserial outer membrane protein proteosomes hydrophobically complexed to native purified bacterial lipopolysaccaride and formulated in accordance with the current invention for mucosal delivery such as via the oral or intranasal route is used as a vaccine. Specifically, a vaccine usinglipopolysaccharides complexed to proteosomes for such mucosal administration induces IgG and IgA antibodies in sera and in respiratory and intestinal fluids. Furthermore, such antibodies are associated with protection against shigella infection and these vaccines are herein demonstrated to protect against mucosal infection with shigella.

Oral or intranasal vaccines using hydrophobic complexes having proteosomes and lipopolysaccharides

An immunogenic complex, essentially consisting of neisserial outer membrane protein proteosomes hydrophobically complexed to native purified bacterial lipopolysaccharide and formulated in accordance with the current invention for mucosal delivery such as via the oral or intranasal route is used as a vaccine. Specifically, a vaccine using shigella lipopolysaccharides complexed to proteosomes for such mucosal administration induces IgG and IgA antibodies in sera and in respiratory and intestinal fluids. Furthermore, such antibodies are associated with protection against shigella infection and these vaccines are herein demonstrated to protect against mucosal infection with shigella.

A continuous method for preparing proteosome-amphiphilic determinant vaccines for parenteral or mucosal administration using diafiltration or ultrafiltration technology. The amphiphilic determinants include lipopolysaccharides from gram negative bacteria, e.g. and . Proteosomes are obtained from group B type 2b meningococci. The active proteosome-amphiphilic determinant complexes (non-covalent complexes) of the vaccine are formed using diafiltration or ultrafiltration to remove the detergent under non-static conditions. The use of diafiltration or ultrafiltration decreases processing time and the opportunity for contamination and further permits the use of ambient temperature and efficient scale-up. In addition, the process permits the reliable and continuous monitoring of the dializate which enhances the efficiency of the entire process. The time of dialysis for the production of a lot of vaccine is reduced from 7-10 days to less than 72 hours and usually less than 48 or 24 hours. The use of the process optimizes the presence of each antigenic component in the preparation of multivalent vaccines.

Methods for the production of non-covalently complexed and multivalent proteosome sub-unit vaccines

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Hampstead, Canada

George H Lowell