Product Pipeline
Product Detail
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.


Clinical Trials
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.


Related News
10/29/2001 Corixa and Wyeth Lederle Vaccines amend agreement
03/27/2000 Corixa and Wyeth Lederle Vaccines expand alliance
06/10/1999 Corixa to acquire Ribi

Publications
Adjuvant activity of monophosphoryl lipid A for nasal and oral immunization with soluble or liposome-associated antigen
2000
Childers, NK, Miller, KL, Tong, G, Llarena, JC, Greenway, T, Ulrich, JT, and Michalek, SM
Infection and Immunity
68/5509-5516
DNA vaccination of mice against rabies virus: effects of the route of vaccination and the adjuvant monophosphoryl lipid A (MPL)
2000
Lodmell Dl, R, Ray, NB, Ulrich, JT, and Ewalt, LC
Vaccine
18/1059-1066
MPL(R) immunostimulant: Vaccine adjuvants: Preparation methods and research protocols
2000
Ulrich, JT and OHagan, DT
Methods in Molecular Medicine
pp. 273-282
3-O-Desacyl monophosphoryl lipid A derivatives: synthesis and immunostimulant activities
1999
Johnson, DA, Keegan, DS, Sowell, CG, Livesay, MT, Johnson, CL, Taubner, LM, Harris, A, Myers, KR, Thompson, JD, Gustafson, GL, Rhodes, MJ, Ulrich, JT, Ward, JR, Yorgensen, YM, Cantrell, JL, and Brookshire, VG
Journal of Medicinal Chemistry
42/4640-4649
Monophosphoryl lipid A (MPL) formulations for the next generation of vaccines
1999
Baldridge, JR and Crane, RT
Methods
19/103-107
Adjuvant activity of monophosphoryl lipid A for nasal and oral immunization with antigen or incorporated into liposomes
1998
Childers, NK, Miller, KL, Martin, M, Greenway, T, Tong, G, Ulrich, JT, and Michalek, SM
Journal of Dental Research
77/582
Cross-clade p17 peptide recognition by antisera to HGP-30, a 30-amino acid synthetic peptide antigen from HIV type 1 p17
1998
Zimmerman, DH, Ulrich, JT, Wright, C, Lloyd, JP, Winship, MD, and Sarin Ps, R
Aids Research and Human Retroviruses
14/741-749
Enhanced immunogenicity of a recombinant genital warts vaccine adjuvanted with monophosphoryl lipid A
1998
Thompson, HSG, Davies, ML, Watts, MJ, Mann, AE, Holding, FP, ONeill, T, Beech, JT, Thompson, SJ, Leesman, GD, and Ulrich, JT
Vaccine
16/1993-1999
Analysis of a monophosphoryl lipid A immunostimulant preparation from Salmonella minnesota R595 by high-performance liquid chromatography
1997
Hagen, SR, Thompson, JD, Snyder, DS, and Myers, KR
J. Chromatogr. A
767/53-61
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