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Adjuvant activity of muramyl dipeptide derivatives to enhance immunogenicity of a hantavirus-inactivated vaccine. 1998

Y C Yoo, and K Yoshimatsu, and Y Koike, and R Hatsuse, and K Yamanishi, and O Tanishita, and J Arikawa, and I Azuma
Institute of Immunological Science, School of Medicine, Hokkaido University, Sapporo, Japan.

The adjuvant effect of two lipophilic derivatives of muramyl dipeptide (MDP), B30-MDP and MDP-Lys(L18), on the ability of an inactivated vaccine of B-1 virus (B-1 vaccine) to induce immune response against Hantavirus causing hemorrhagic fever with renal syndrome (HFRS) was examined. When mice were immunized subcutaneously (s.c.) twice at 2-week intervals with B-1 vaccine admixed with or without 100 micrograms mouse-1 of B30-MDP (B-1/B30-MDP) or MDP-Lys(L18) [B-1/MDP-Lys(L18)], mice immunized with B-1/B30-MDP as well as B-1/MDP-Lys(L18) showed significantly higher indirect fluorescent antibody (IFA) titers against HFRS virus than mice immunized with B-1 vaccine alone. Both mice treated with B-1/B30-MDP and B-1/MDP-Lys(L18) also exhibited significantly higher neutralizing antibody titers against HFRS virus than mice immunized with B-1 vaccine alone during 3-9 weeks after the primary immunization. The evaluation of antibody-producing cells by enzyme-linked immunospot (ELISPOT) assay on week 4 revealed that both MDP derivatives enhanced the number of HFRS virus-specific IgG1 and IgM antibody-producing cells. Furthermore, mice treated with B-1/B30-MDP as well as B-1/MDP-Lys(L18) showed a higher level of Th-2 type cytokines, IL-4 and IL-6, in sera than mice treated with B-1 alone. In an in-vitro analysis of T lymphocyte proliferation to baculovirus-expressed recombinant nucleocapsid protein (rNP) of Hantaan 76-118 strain, the splenocytes of mice treated with B-1/B30-MDP and B-1/MDP-Lys(L18) on week 4 showed a significantly higher proliferating activity than those treated with B-1 vaccine alone. In addition, when mice were immunized once with B-1 vaccine admixed with or without B30-MDP and MDP-Lys(L18) and followed by intrafootpad (i.f.) injection of B-1 vaccine on day 7, mice immunized with B-1/B30-MDP and B-1/MDP-Lys(L18) induced a higher delayed-type hypersensitivity (DTH) reaction than mice immunized with B-1 vaccine alone. These results suggest that B30-MDP and MDP-Lys(L18) are useful immunoadjuvants to enhance the ability of inactivated B-1 vaccine to induce a humoral and cellular response to HFRS virus.

UI MeSH Term Description Entries
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D002522 Chlorocebus aethiops A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research. African Green Monkey,Cercopithecus aethiops,Cercopithecus griseoviridis,Cercopithecus griseus,Cercopithecus pygerythrus,Cercopithecus sabeus,Cercopithecus tantalus,Chlorocebus cynosuros,Chlorocebus cynosurus,Chlorocebus pygerythrus,Green Monkey,Grivet Monkey,Lasiopyga weidholzi,Malbrouck,Malbrouck Monkey,Monkey, African Green,Monkey, Green,Monkey, Grivet,Monkey, Vervet,Savanah Monkey,Vervet Monkey,Savannah Monkey,African Green Monkey,Chlorocebus cynosuro,Green Monkey, African,Green Monkeys,Grivet Monkeys,Malbrouck Monkeys,Malbroucks,Monkey, Malbrouck,Monkey, Savanah,Monkey, Savannah,Savannah Monkeys,Vervet Monkeys
D005260 Female Females
D006476 Orthohantavirus A genus of the family BUNYAVIRIDAE causing HANTAVIRUS INFECTIONS, first identified during the Korean war. Infection is found primarily in rodents and humans. Transmission does not appear to involve arthropods. HANTAAN VIRUS is the type species. Dobrava-Belgrade Virus,Hantavirus,Andes Hantavirus,Andes Virus,Andes Hantaviruses,Dobrava Belgrade Virus,Hantavirus, Andes,Hantaviruses,Hantaviruses, Andes,Orthohantaviruses
D000119 Acetylmuramyl-Alanyl-Isoglutamine Peptidoglycan immunoadjuvant originally isolated from bacterial cell wall fragments; also acts as pyrogen and may cause arthritis; stimulates both humoral and cellular immunity. Mur-NAc-L-Ala-D-isoGln,Muramyl Dipeptide,Acetylmuramyl Alanyl Isoglutamine,N-Acetyl-Muramyl-L-Alanyl-D-Glutamic-alpha-Amide,N-Acetylmuramyl-L-Alanyl-D-Isoglutamine,Alanyl Isoglutamine, Acetylmuramyl,Dipeptide, Muramyl,Isoglutamine, Acetylmuramyl Alanyl,Mur NAc L Ala D isoGln,N Acetyl Muramyl L Alanyl D Glutamic alpha Amide,N Acetylmuramyl L Alanyl D Isoglutamine
D000276 Adjuvants, Immunologic Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Immunoactivators,Immunoadjuvant,Immunoadjuvants,Immunologic Adjuvant,Immunopotentiator,Immunopotentiators,Immunostimulant,Immunostimulants,Adjuvant, Immunologic,Adjuvants, Immunological,Immunologic Adjuvants,Immunological Adjuvant,Adjuvant, Immunological,Immunological Adjuvants
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000914 Antibodies, Viral Immunoglobulins produced in response to VIRAL ANTIGENS. Viral Antibodies
D014709 Vero Cells A CELL LINE derived from the kidney of the African green (vervet) monkey, (CHLOROCEBUS AETHIOPS) used primarily in virus replication studies and plaque assays. Cell, Vero,Cells, Vero,Vero Cell

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