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MPL® adjuvant, our flagship adjuvant, is a derivative of the lipid A molecule found in gram-negative bacteria, and has been observed to be a potent immunostimulant. Licenses for MPL adjuvant have been granted to several affiliates of GSK and to Wyeth-Lederle Vaccines for development in over 20 disease targets. Vaccines that incorporate MPL adjuvant have completed or are now in late-stage clinical trials to protect against infection from:
- herpes virus;
- hepatitis B virus;
- human papilloma virus;
- malaria; and
- respiratory syncytial virus.
Technical Description
MPL adjuvant is a proprietary form of monophosphoryl lipid A, a derivative of bacterial endotoxin, one of the most potent immunostimulants known. Prepared from a heptoseless mutant of Salmonella minnesota, MPL is chemically similar to lipid A but lacks an acid-labile phosphoryl group and a base-labile acyl group. MPL retains the beneficial biological activities of lipid A but with a safety profile suitable for evaluation in pediatric applications.
MPL may be a key component of vaccines using technologies such as recombinant and synthetic antigens. Although vaccines incorporating these antigens are safer than previous attenuated or killed whole-cell vaccines, many of them are poorly immunogenic in the absence of a potent adjuvant. MPL has demonstrated utility with peptide, bacterial sub-unit and synthetic polysaccharide antigens. Vaccines for infectious diseases and allergy desensitization containing this microbially derived adjuvant have demonstrated safety and efficacy in human clinical trials involving thousands of doses. Humoral, cell-mediated and mucosal immunity can be stimulated by altering formulations and delivery routes. Corixa produces MPL in a GMP manufacturing facility, and offers extensive regulatory experience and formulation support to our vaccine development partners.
Clinical Experience with MPL
Corixa and its partners have extensive human clinical experience with MPL. Vaccines containing this microbially derived adjuvant have been shown to be well-tolerated and active in human clinical trials involving more than 10,000 subjects. A variety of antigens have been used successfully with MPL, including recombinant proteins, peptides, bacterial sub-units, polysaccharides, polysaccharide conjugates and tumor cell lysates. Diseases targeted have included allergies, hepatitis B, genital herpes, genital warts, malaria, RSV and certain pediatric vaccines.
Mechanism of Action
MPL activates cells of the monocyte/macrophage lineage and stimulates release of several cytokines, including IL-1, IL-12, TNFa and GM-CSF. Presumably through the action of these cytokines, lymphoid and antigen-presenting cells, including dendritic cells, are recruited to the local lymphoid organs where efficient immuno-enhancing cellular interactions can take place. These initial events mediated by MPL induce a strong TH1-type of cellular response characterized by increased production of IFN-g and IL-2. In turn, IFN-g promotes the production of complement fixing antibodies (i.e., IgG2a in the mouse), a hallmark of responses mediated by MPL.
MPL enhances immune responses to a variety of viral and bacterial antigen types, including peptides, proteins, polysaccharides and tumor cell lysates. Antigens successfully tested in preclinical studies include hepatitis B surface antigen, tetanus toxoid, trivalent split influenza, and a recombinant protein derived from the saliva-binding region of an adhesion protein of Streptococcus mutans. MPL produced striking results in studies with capsular polysaccharide antigens from organisms such as Hemophilus influenza b, several strains of pneumococcal bacteria and the Vi antigen from Salmonella typhi. |
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GSK recently completed a Phase III clinical trial of a genital herpes vaccine containing Corixa's MPL adjuvant.
This document is intended to provide only an overview of Corixa's product candidates. For complete information, please refer to the company's Annual Report on Form 10-K, press releases and other public information. |
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