      Document 0074
 DOCN  DRG0074
 UNIQUE IDENTIFIER        DRG-0173
 NAME OF SUBSTANCE        Monophosphoryl lipid A [Infect Immu 1990
                          Mar;58(3)]
 SYNONYMS                 MPL [Infect Immu 1990 Mar;58(3)]
 SYNONYMS                 Lipid A MP [MeSH]
 SYNONYMS                 MPLA [Infect Immu 1986 Sep;58(3)]
 PROTOCOL ID NUMBERS      NIAID VEU 015
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Monophosphoryl lipid A has
                          been shown to be a potent immunologic
                          adjuvant. The mechanism in which adjuvants
                          augment vaccine immunogenicity may include 1)
                          the prolongation of antigen exposure to
                          antigen presenting cells by the creation of a
                          depot at the site of injection, 2) the
                          activation of antigen presenting cells, such
                          as monocytes or macrophages, to release
                          cytokines that can promote T-cell help for B
                          cell and CTL response, 3) the introduction of
                          antigen into the MHC Class I processing
                          pathway. As a result, the adjuvant may induce
                          a more favorable antibody response with high
                          titers, which appear earlier in the course of
                          immunization and persist over time, as well
                          as increase memory responses and CD8+ MHC
                          Class I-restricted CTL. Animal studies
                          suggest monophosphoryl lipid A increases
                          antibody formation by inducing the helper T
                          cell population to secrete interferon gamma.
                          The latter activates the macrophage to
                          secrete increased levels of interleukin 1,
                          thereby resulting in increased responsiveness
                          throughout the ensuing sequence of cellular
                          and molecular events leading to antibody
                          synthesis. [Adv Exp Med Biol 1990; No 256 p
                          567-79] [NIAID VEU 015]
 DISEASES STUDIED/TREATED Primary HIV infection: as a vaccine adjuvant
                          for the enhancement of the immune response
                          [NIAID VEU 015]
 CLASSIFICATION CODE      Adjuvant [J Immunol 1991 Oct 1; 147(7)]
 CLASSIFICATION CODE      Immunostimulant [NIAID VEU 015]
 OTHER MAJOR USES         An immunological adjuvant; induction of
                          endotoxicn tolerance with monophosphoryl
                          lipid A improves survival from peritonitis
                          [NIAID VEU 015] [J Lab Clin Med 1994
                          Jan;123(1)]
 ADVERSE EFFECTS          Mild to moderate symptoms include headache,
                          chills, myaglia, and pain at the site of
                          injection. [NIAID VEU 015]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A monophosphorylated lipid;
                          a non-toxic derivative of lipid A [NIAID VEU
                          015] [Infect Immun 1986 Apr;52(1)]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Vials containing 100 mcg per ml.
                          [NIAID VEU 015]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intramuscular injection.
                          [NIAID VEU 015]
 SUBSTANCE DELIVERY DATA  STORAGE INSTRUCTIONS: Vials should be stored
                          at 2-6 C. [NIAID VEU 015]
 MANUFACTURERS            RIBI ImmunoChem Research Inc
 REFERENCES               Courtois G, Benit L, Mikaeloff Y, Pauchard M,
                          Charon M, Varlet P, Gisselbrecht S.
                          Constitutive activation of a variant of the
                          env-mpl oncogene product by disulfide-linked
                          homodimerization. J Virol. 1995
                          May;69(5):2794-800.
 REFERENCES               Schultz N, Oratz R, Chen D,
                          Zeleniuch-Jacquotte A, Abeles G, Bystryn JC.
                          Effect of DETOX as an adjuvant for melanoma
                          vaccine. Vaccine 1995 Apr;13(5):503-8.
 REFERENCES               Myers KR, Beining P, Betts M, Snippe H, Inman
                          J, Golding B. Monophosphoryl lipid A behaves
                          as a T-cell-independent type 1 carrier for
                          hapten-specific antibody responses in mice.
                          Infect Immun. 1995 Jan;63(1):168-74.
 REFERENCES               Hoffman SL, Edelman R, Bryan JP, Schneider I,
                          Davis J, Sedegah M, Gordon D, Church P, Gross
                          M, Silverman C, et al. Safety,
                          immunogenicity, and efficacy of a malaria
                          sporozoite vaccine administered with
                          monophosphoryl lipid A, cell wall skeleton of
                          mycobacteria, and squalane as adjuvant. Am J
                          Trop Med Hyg 1994 Nov;51(5):603-12.
 REFERENCES               Vaslin B, Le Grand R, Vogt G, Benveniste O,
                          Gras G, Roques P, Stoeckel P, Salk PL, Salk
                          J, Dormont D. Induction of humoral and
                          cellular immunity to simian immunodeficiency
                          virus: what are the requirements for
                          protection? Vaccine. 1994 Sep;12(12):1132-40.
 REFERENCES               Johnson AG. Molecular adjuvants and
                          immunomodulators: new approaches to
                          immunization. Clin Microbiol Rev 1994
                          Jul;7(3):277-89.
 REFERENCES               Ravindrath MH, Brazeau SM, Morton DL.
                          Efficacy of tumor cell vaccine after
                          incorporating monophosphoryl lipid A (MPL) in
                          tumor cell membranes containing
                          tumor-associated ganglioside. Experientia.
                          1994 Jul 15;50(7):648-53.
 REFERENCES               Hui GS. Liposomes, muramyl dipeptide
                          derivatives, and nontoxic lipid A derivatives
                          as adjuvants for human malaria vaccines. Am J
                          Trop Med Hyg. 1994;50(4 Suppl):41-51.
 REFERENCES               Zhou F, Huang L. Monophosphoryl lipid A
                          enhances specific CTL induction by a soluble
                          protein antigen entrapped in liposomes.
                          Vaccine. 1993;11(11):1139-44.
 REFERENCES               Friede M, Muller S, Briand JP, Van
                          Regenmortel MH, Schuber F. Induction of
                          immune response against a short synthetic
                          peptide antigen coupled to small neutral
                          liposomes containing monophosphoryl lipid A.
                          Mol Immunol; VOL 30, ISS 6, 1993, P539-47.
 ENTRY MONTH              9306
 LAST REVISION DATE       960405
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
