      Document 0073
 DOCN  DRG0073
 UNIQUE IDENTIFIER        DRG-0174
 NAME OF SUBSTANCE        Liposome-encapsulated monophosphoryl lipid A
                          [NIAID VEU 015]
 PROTOCOL ID NUMBERS      NIAID VEU 015
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: The mechanisms 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. Encapsulation of
                          poorly immunogenic circumsporozoite protein
                          repeat peptides in monophosphoryl lipid A
                          containing liposomes is a successful adjuvant
                          strategy in humans for inducing high levels
                          of specific antibody production. The
                          mechanism of the adjuvant action of liposomal
                          lipid A is partly due to increased antigen
                          presentation by macrophages and partly due to
                          recruitment of an increased number of
                          macrophages serving as antigen-presenting
                          cells. [NIAID VEU 015] [Proc Natl Acad Sci
                          USA 1992 Jan 1;89(1)] [Infect Immun 1992
                          Jun;60(6)]
 DISEASES STUDIED/TREATED Primary HIV infection: as a vaccine adjuvant
                          for the enhancement of the immune response
                          [NIAID VEU 015]
 CLASSIFICATION CODE      Adjuvant [Proc Natl Acad Sci USA 1992 Jan
                          1;89(1)]
 CLASSIFICATION CODE      Immunostimulant [NIAID VEU 015]
 ADVERSE EFFECTS          Moderate but acceptable transient local
                          reactogenicity was noted at high doses of the
                          vaccine formulation, but little or no
                          systemic toxicity was seen despite doses up
                          to 2200 mcg. [Proc Natl Acad Sci USA 1992 Jan
                          1;89(1)]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Liposomes made of
                          phospholipids and cholesterol that contain
                          monophosphoryl lipid A [NIAID VEU 015]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Vial with 8.8 mg MPL per ml.
                          [NIAID VEU 015]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intramuscular injection.
                          [NIAID VEU 015]
 SUBSTANCE DELIVERY DATA  STORAGE INSTRUCTIONS: Store at 4 C. [NIAID
                          VEU 015]
 MANUFACTURERS            Walter Reed Army Institute of Research
 REFERENCES               White WI, Cassatt DR, Madsen J, Burke SJ,
                          Woods RM, Wassef NM, Alving CR, Koenig S.
                          Antibody and cytotoxic T-lymphocyte responses
                          to a single liposome-associated peptide
                          antigen. Vaccine 1995 Aug;13(12):1111-22.
 REFERENCES               Alving CR. Liposomal vaccines: clinical
                          status and immunological presentation for
                          humoral and cellular immunity. Ann N Y Acad
                          Sci. 1995 May 31;754:143-52.
 REFERENCES               Benkirane N, Guichard G, Van Regenmortel MH,
                          Briand JP, Muller S. Cross-reactivity of
                          antibodies to retro-inverso peptidomimetics
                          with the parent protein histone H3 and
                          chromatin core particle. Specificity and
                          kinetic rate-constant measurements. J Biol
                          Chem 1995 May 19;270(20):11921-6.
 REFERENCES               Ravindranath MH, Morton DL, Irie RF.
                          Attachment of monophosphoryl lipid A (MPL) to
                          cells and liposomes augments antibody
                          response to membrane-bound gangliosides. J
                          Autoimmun 1994 Dec;7(6):803-16.
 REFERENCES               Ravindranath 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               Wassef NM, Alving CR, Richards RL. Liposomes
                          as carriers of vaccines. Immunomethods. 1994
                          Jun;4(3):217-22.
 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               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. 1993 Apr;30(6):539-47.
 REFERENCES               Alving CR. Lipopolysaccharide, lipid A, and
                          liposomes containing lipid A as immunologic
                          adjuvants. Immunobiology. 1993
                          Apr;187(3-5):430-46.
 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.
 ENTRY MONTH              9306
 LAST REVISION DATE       960403
 

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