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Response to influenza vaccine in adjuvant 65-4.

A comparison was made of the antibody response and subjective reactions to zonally-purified influenza vaccine in aqueous suspension and in peanut oil adjuvant 65-4. Both preparations contained 700 CCA units of A/Aichi/2/68, and 300 CCA units of B/Mass/1/71. Subjective reactions were recorded by asking the volunteers to complete a record daily for 5 days. Pain at the injection site was recorded by 64 per cent of the recipients of the oil adjuvant vaccine compared with 35 per cent of the aqueous recipients, but local redness was more frequent after aqueous vaccine. Systemic symptoms was recorded a little more frequently after aqueous than oil adjuvant vaccine. When measured 71/2 weeks after a single dose of vaccine, the HAI geometric mean antibody titre (G.M.T) to the A/Hong Kong/1/68 antigen (antigenically similar to the A/Aichi/2/68 antigen in the vaccine) increased 2-7 fold after aqueous and 16-4 fold after adjuvant vaccine. Sixty-two weeks after vaccination the antibody titres remained higher in those given adjuvant vaccine. The G.M.T. to B/Mass/1/71 increased 1-9 fold 71/2 weeks after aqueous vaccine and 3-7 fold after adjuvant vaccine. The antibody response to both influenza A and B antigens was broader in the recipients of adjuvant vaccine. The G.M.T. to A/England/42/72 increased 2-8-fold after aqueous and 13-fold after adjuvant vaccine; and to B/England/847/73 it increased 1-3-fold after aqueous and 1-9-fold after adjuvant vaccine.

Adjuvants, Immunologic

The adjuvant activity of mycobacterial RNA preparations and synthetic polynucleotides for induction of delayed hypersensitivity to purified protein derivative in guinea pigs.

The adjuvant activity of mycobacterial RNA and synthetic polynucleotides for the induction of delayed hypersensitivity to PPD was determined. It was shown that when mycobacterial RNA or synthetic polynucleotides are injected together with purified protein derivative (PPD), delayed hypersensitivity to PPD developed as compared to no detectable delayed response when PPD was administered alone without adjuvant into guinea pigs. Four different criteria were employed to detect delayed hypersensitivity responses. These were the time, appearance, and magnitude of dermal reactions, histologic examination of dermal sections, passive transfer of sensitivity with sensitized spleen cells and the elaboration of migration inhibitory factor (MIF) by sensitized spleen cells. When synthetic polynucleotides were used as adjuvants and were injected into guinea pigs in combination with PPD, dermal reactions as well ad MIF assays gave evidence that these animals exhibited delayed-type hypersensitivity. Poly U alone exhibited adjuvant activity for induction of delayed hypersensitivity to PPD. Trypsin and pronase treatment did not affect the adjuvant activity of mycobacterial RNA whereas KOH treatment completely abolished any adjuvant effect, suggesting that ribosomal protein did not contribute to the adjuvant characteristics of mycobacterial RNA. Titration experiments indicated that the adjuvant activity of mycobacterial RNA was greater than that of poly A:U.

Adjuvants, Immunologic

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

A serological comparison of Pasteurella haemolytica vaccines containing different adjuvants.

Five adjuvants were compared for their ability to enhance the serological response of sheep to capsule extract of Pasteurella haemolytica biotype A serotype 6. Vaccines of this antigen were inoculated with incomplete Freund's adjuvant, complete Freund's adjuvant, incomplete Freund's adjuvant containing a water soluble extract of Mycobacterium tuberculosis, aluminium hydroxide gel or a combination of aluminium hydroxide gel and incomplete Freund's adjuvant. This latter vaccine induced significantly higher titres of antibody as measured by an indirect haemagglutination test than did any of the other vaccines. The aluminium hydroxide gel alone was shown to be the poorest adjuvant. The local reactions at the sites of inoculations produced by the aluminium hydroxide gel in incomplete Freund's adjuvant vaccine were not severe and were not detectable beyond one month after vaccination in the majority of the sheep.

Adjuvants, Immunologic

Immunological studies on the original endotoxin protein (OEP) of Pseudomonas aeruginosa. Adjuvant effect of OEP in vivo.

OEP--Original Endotoxin Protein--is a protein moiety of endotoxin of Pseudomonas aeruginosa. An adjuvant action of OEP was investigated in mice immunized with sheep red blood cells (SRBC). Several features characteristic of the adjuvant action of OEP have been revealed; OEP shows no effect on simultaneous treatment with the antigen, and is most effective on successive treatments given after SRBC. The effective dosages of OEP as an adjuvant were in the range of 10 to 100 mug per mouse. Experimental data suggested that OEP might enhance the antibody production in its early phase. The adjuvant action of OEP was lost in mice pretreated with large dosage of OEP; OEP-tolerance could be induced to its adjuvant action. The mechanism of the adjuvant action of OEP was discussed comparing with other adjuvants.

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.

Adult

A review of the current status of oil adjuvants in foot--and--mouth disease vaccines.

Review of lipovaccines since 1916, including oil adjuvants (1935-1943) and the two Freund's adjuvants. The first oil-adjuvanted vaccines appeared in 1961. Criticism of the water-in-oil and oil-in-water vaccines and description of the mineral oil adjuvants which are available today. The authors set forth the advantages of oil adjuvants and secondary reactions which might occur; they are particularly interested in the foot-and-mouth disease vaccine intended for use in swine and express their regret that no method of standardization has yet been adopted for oil-adjuvanted vaccines which are promising but which necessitate still further study.

Adjuvants, Immunologic

Protection induced by inactivated influenza virus vaccines with polymethylmethacrylate adjuvants.

Nanocapsules from a copolymer of polymethylmethacrylate and polyacrylamide were tested for adjuvant activity in mouse protection experiments with inactivated influenza virus as antigen. Viruses were either adsorbed on the capsules after polymerization or added to the monomers and incorporated by copolymerization after X-ray initiation. Both preparations showed enhanced immunity as compared to fluid vaccine, if the adjuvant content was 1%. The adjuvant effect was comparable to that caused by the mineral adjuvant Al(OH)3. After dilution of the polymer the adjuvant effect was lost. Such synthetic polymers at suitable concentrations could serve as alternatives to mineral adjuvants.

Acrylamides

Water-soluble adjuvant obtained from Bacterionema matruchotii.

The adjuvant effect of a butanol-extracted water-soluble adjuvant (bu-WSA) obtained from Bacterionemia matruchotii, a gram-positive oral bacteria, was studied on the antibody response at the plaque-forming cell (PFC) level in murine spleens. Intraperitoneal injection of Bu-WSA caused significant increase in direct PFC numbers in spleens 1 to 3 days after the antigenic stimulation with sheep erythrocytes (SRBC). Injection of 100 to 800 microgram of Bu-WSA was effective, and 400 microgram of Bu-WSA seemed to be the optimum for induction of the adjuvant effect. The adjuvant effect was strongest when Bu-WSA was injected at the same time as the SRBC, but some effect was still observed when Bu-WSA was injected 7 days before or 1 day after the immunization. The adjuvant effect of Bu-WSA was greatest at high dose of antigen. The mice injected with Bu-WSA at the time of priming SRBC and then immunized with trinitrophenylated SRBC showed greater anti-trinitrophenyl PFC response than controls without the injection of Bu-WSA. These findings suggest that a part of the adjuvant effect of Bu-WSA depends on thymic cell function and another part does not.

Actinomycetaceae

Adjuvant regulation of T cell function.

The effect of complete Freund's adjuvant (CFA) on distinct T cell functions was investigated. Adjuvant was found to suppress the generation of cytolytic T cells in vivo when mixed with allogeneic P815 cells before immunization of C57BL/6 mice. Inoculation of the mice with either adjuvant or adjuvant emulsified with allogeneic cells resulted in whole splenic populations or immunoabsorbent-purified T cells that did not generate cytolytic activity in vitro against allogeneic cells. Mixing T cells from normal and adjuvant-treated mice before in vitro sensitization resulted in suppression of lytic activity. However, memory T cells were not subject to the same suppressive regulation as were precytotoxic T cells since adjuvant had no effect on subsequent boosting of memory.

Animals