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Kinetics of the humoral and cellular immune response of guinea pigs after injection of the synthetic adjuvant N-acetylmuramyl L-alanyl-D-isoglutamine: comparison with Freund complete adjuvant.

We studied the time course of humoral and cellular immunity of guinea pigs injected with the synthetic adjuvant N-acetylmuramyl L-alanyl-D-isoglutamine (MDP Pasteur, 10 microgram) in Freund incomplete adjuvant; the kinetics were compared with those obtained with Freund complete adjuvant (50 microgram of whole Mycobacterium butyricum). The antibody response to ovalbumin was faster and higher with MDP, but dropped sooner to a low level; the secondary response was, however, again higher for MDP than for Freund complete adjuvant. Cellular immunity, as measured by delayed hypersensitivity, and migration inhibition factor production werepositive for both adjuvants. The same response was followed in animals injected with MDPA, the nonamidated analog of MDP; the same kinetics as for Freund incomplete adjuvant were obtained for the primary response, but the secondary response was stronger and gave a positive delayed hypersensitivity reaction.

Adjuvants, Immunologic

Studies on adjuvants for human prophylactics. II. Influence of the route of injection on the activity of adjuvants to tetanus toxoid in guinea pigs.

The effects of the route of the injection and adjuvants on the immune response of guinea pigs were investigated at various stages of immune response to tetanus toxoid. Delayed-type hypersensitivity (DH) was observed as the first immune response to the toxoid before initiation of antitoxin production. The DH reaction was weak when plain toxoid was administered subcutaneously. Water-in-oil in water (w/o/w) enhanced greatly the reactivity of the immunized animals; pertussis vaccine, endotoxin and aluminium showed adjuvanticities in this order. The foot pad (fp) injection of plain toxoid promoted remarkably the induction of DH. The reactivity was enhanced considerably by w/o/w and to a less extent by aluminium. However, pertussis vaccine showed an adverse effect on DH by the fp route. Active cutaneous anaphylaxis (ACA) induced by the subcutaneous route was enhanced by w/o/w, endotoxin, pertussis vaccine and, to a less extent, by aluminium. The fp route compared with the sc route enhanced ACA by plain toxoid; w/o/w and aluminium but not endotoxin and the vaccine showed adjuvanticities. The influences of adjuvants and the route of injection on Arthus reactions were inconsistent. The effect of adjuvants on antitoxin production was quite different from that on DH when antitoxin was produced abundantly. Aluminium showed consistently a potent adjuvanticity, but activities of w/o/w, endotoxin and pertussis vaccine were inconsistent 4-6 weeks after the primary stimulus by the subcutaneous route. The adjuvant effect became less significant in the secondary response. The fp route was more favorable for antitoxin production than the subcutaneous route with most adjuvants except pertussis vaccine added to tetanus toxoid. Antitoxin production by plain toxoid was very poor when administered intraperitoneally; aluminium and w/o/w but not endotoxin showed a remarkable adjuvanticity for the antitoxin production.

Adjuvants, Immunologic

Studies about the adjuvant activity of saponin fractions in foot and mouth disease vaccine. III. Comparison of the irritant, adjuvant and hemolytic activities of six commercial saponins and their hemolytic fractions obtained by chromatography on sephadex G 100.

12 experimental vaccines were prepared to compare the irritant and adjuvant activity in cattle of 6 commercial saponin preparations and their hemolytic fractions. It is still not known if a single substance is responsible for the irritant, adjuvant and hemolytic activities of the saponin preparations. The quantities of saponin added were standardised on the base of a constant hemolytic activity rather than on a weight of powder per dose of vaccine base. A FMD vaccine was used to reveal the adjuvant activity. It was concluded that the irritation is related to the hemolytic activity and not to the weight of powder. Irritation is slightly reduced when a toxic effect appears. The adjuvant activity was higher for untreated saponin preparations with high hemolytic activity used at low dose and for one of the chromatographic saponin fractions. The adjuvant activity is reduced when toxic effect appear. Toxicity of less hemolytic saponins used at high dose is removed by chromatography. Highly hemolytic saponins used at low dose become toxic after chromatographic treatment.

Adjuvants, Immunologic

[Comparison of a bivalent anti-foot-and-mouth disease vaccine with oil adjuvant to a vaccine with DEAE-dextran adjuvant in swine].

The report compares the compatibility, efficacity and serology response of two bivalent anti-foot-and-mouth disease vaccines (OC). One is oil-adjuvanted and the other based on diethyl-amino-ethyl-dextran (DEAE-Dextran). After vaccination no general clinical or local reactions are normally observed. Tissular reactions at the inoculation site are more severe with the oil-adjuvanted vaccine than with the DEAE-Dextran vaccine. Meat inspection, about three months after injection of the vaccine, showed the lesions to be in regression and negligible. The control of activity has been performed by the virulence test. For the oil-adjuvanted vaccine, protection against O1-Lausanne, 5, 21 and 90 days after vaccination is 90%, 80-100% and 55% respectively. For the DEAE-Dextran vaccine, these levels of protection are 80% after 5 days and 20-70% after 21 days. The percentage of swine protected against C-Noville 35 days after vaccination is 100% for the oil-adjuvanted vaccine and 70% for the DEAE-Dextran vaccine. The evolution of the amount of serum antibodies was followed for three months by the method of seroneutralization on cell cultures.

Adjuvants, Immunologic

Lysolecithin analogs as adjuvants in delayed-type hypersensitivity in mice. I. Characterization of the adjuvant effect.

The adjuvant activity of 5 different lysolecithin analogs (LLA) has been studied in delayed-type hypersensitivity (DTH) using fowl gamma globulin, bovine serum albumin and the terpolymer L-glutamic acid 60-L-alanine30-L-tyrosine10(GAT), as antigens. Increased DTH responses, by factors of 1.8--2.0 in CBA and BALB/c mice, showed that LLA are immunopotentiators if given intraperitoneally (i.p.) or subcutaneously (s.c.) together with the antigen. The concentration range, within which LLA are active, is limited to 10--20 micrograms/mouse s.c. and 100--300 micrograms/mouse i.p. Adjuvanticity was tested as a function of the LLA structure. The most pronounced immunopotentiation was obtained with racemic 1-octadecyl-2-methylglycero-3-phosphorylcholine (ET18-O-CH3). The LLA became less active with decreasing numbers of C atoms in the alkyl chain.

Adjuvants, Immunologic

Adjuvant and immunostimulating activities (in the absence of freund's incomplete adjuvant) of chemically modified low molecular weight mycobacterial peptidoglycans.

Relatively low molecular weight peptidoglycan fragments extracted from two strains of Mycobacterium tuberculosis var. hominis were chemically coupled with lauric acid. The fatty acid conjugates were compared with the native substances with respect to some immunopotentiating activities. In vitro, the mitogenic effect on murine spleen lymphocytes was significantly enhanced following conjugation. One of the lauric acid conjugates stimulated, upon intravenous administration in mice, the formation of antibody-producing cells in the spleen, while the native substance was devoid of such activity. In adjuvanticity tests performed in the guinea pig in the absence of mineral oil, the fatty acid conjugates generally exerted a higher adjuvant effect on antibody production or on delayed type hypersensitivity reactions than did the native preparations.

Adjuvants, Immunologic

[Interactions between macromolecular adjuvants and drugs. Part 17: On the effect of macromolecular adjuvants on the dissolution rate of chlorpromazine from dosage forms (author's transl)].

The determination of the dissolution rate of chlorpromazine from tablets and triturations containing macromolecular adjuvants by means of a modification of the flow-through type cell according to Langenbucher evidenced a decrease in the dissolution rate produced by polyvinylpyrrolidone, methyl-cellulose and hydroxyethyl-cellulose. It was found that the decrease in the dissolution rate is not due to the confirmed, relatively marked tendency of chlorpromazine to form complexes, but to gel formation.

Adjuvants, Pharmaceutic

Adjuvant properties of Micropolyspora faeni.

The adjuvant properties of Micropolyspora faeni, an important source of antigenic material in the production of farmer's lung, were evaluated by comparing antibody- and cell-mediated immune responses of rabbits to bovine serum albumin (BSA) incorporated in complete Freund's adjuvant (CFA), incomplete Freund's adjuvant (IFA) and incomplete Freund's adjuvant with 5-10 mg/ml homogenized M. faeni (MFA). Rabbits immunized with BSA in CFA or MFA developed significantly increased antigen-induced macrophage migration inhibition, lymphocyte stimulation, and delayed skin reactivity when compared to those immunized with BSA in IFA. No similar adjuvant effect on specific antibody production was observed in rabbits immunized using BSA in MFA. These data suggest that M. faeni can act as a selective immunologic adjuvant for delayed hypersensitivity. This adjuvant property might be important in the induction of mononuclear cell infiltrates seen in human hypersensitivity pneumonitis.

Adjuvants, Immunologic

An adjuvant database for preclinical evaluation of vaccines and immunotherapeutics.

Adjuvants are immunostimulators used to enhance vaccine efficacy against infectious diseases. However, current methods for evaluating their efficacy and safety are limited, hindering large-scale screening. To address this, we developed a prototype Adjuvant Database (ADB) containing transcriptome data, generated using the same protocols as the widely used Open TG-GATEs (OTG) toxicogenomics database, covering 25 adjuvants across multiple species, organs, time points, and doses. This enabled cross-database integration of ADB and OTG. Transcriptomic patterns successfully distinguished each adjuvant regardless of organs or species. Using both databases, we built machine learning models to predict adjuvanticity and hepatotoxicity. Notably, we identified colchicine's adjuvant activity and FK565's liver toxicity through data-driven analysis. Overall, ADB combined with OTG offers a framework for transcriptomics-based, data-driven screening of adjuvant candidates.

Animals

Transcriptomic and proteomic signatures following AS03-adjuvanted Influenza A/H7N9 vaccine.

INTRODUCTION: Vaccines targeting avian influenza virus A/H7N9 are poorly immunogenic. While the immune responses can be improved with oil-in-water emulsion adjuvants such as Adjuvant System 03 (AS03), the cellular mechanisms underpinning the adjuvant effect are incompletely characterized and poorly understood. METHODS: We enrolled 30 healthy adult participants and used RNA sequencing and quantitative proteomics to characterize the response to two doses of the influenza A/H7N9 vaccine, with and without AS03, in six immune cell types. These responses were compared to those seen after administration of an unadjuvanted seasonal in uenza A/H3N2 variant vaccine to identify signatures unique to adjuvanted influenza vaccines and correlated with later antibody responses. Transcriptomic and proteomic analyses revealed that. RESULTS: AS03-adjuvanted vaccine was associated with upregulation of immune pathways in innate immune cells within 24h following vaccination for phagocytosis, antigen presentation and processing, inflammasome activation, NK-cell mediated cytotoxicity, IgA production, and interferon-response pathways. Moreover, while major histocompatibility complex (MHC I and II) upregulation was observed across multiple immune cell types, MHCII gene transcription was also increased in the neutrophil compartment, generating the hypothesis that neutrophils may play a more important role in antigen presentation than previously understood. DISCUSSION: Taken together, these data provide a more complete mechanistic understanding of oil-in-water adjuvants and their role in enhancing the immune response for pandemic influenza preparedness. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT02921997?term=NCT02921997&viewType, idientifier NCT02921997.

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