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At least 19 recordsLinked to original sources

PubMed1975

The mode of action of immunological adjuvants. I. A new method to assess the adjuvant effect of substances as represented by mycobacterial adjuvants.

When mice were sensitized with sheep red blood cells (SRBC), the addition of adjuvant-active substances to the sensitizing antigen resulted in a highly significant increase in the mean diameter of plaques developed by spleen cells as measured by Jerne's plaque technique. The increase in plaque diameter was found to be a good measure for the adjuvant effect of such substances as mycobacterial adjuvants, because the phenomenon is specific, reproducible, sensitive and can be tested using a few number of mice.

Adjuvants, Immunologic↗

PubMed1978

Mode of action of immunological adjuvants: some physicochemical factors influencing the effectivity of polyacrylic adjuvants.

The adjuvant effects of different polyacrylic products and monomers were tested. Influenza vaccine was used as a model antigen. Addition of monomers resulted in a decrease in the antibody response, though adjuvant activity of the monomers should be expected according to some theories on adjuvant action. The particle size of the polymer adjuvants proved to be a very important parameter for adjuvant activity. Particles of 0.1 to 0.2 micron yielded a good adjuvant effect, whereas conglomerates or particles bigger than 0.5 micron yielded only poor or no adjuvant effects. The adjuvant effect of 0.1- to 0.2-micron particles was much more reproducible than rat of Al(OH)3. Attention is drawn to the importance of using physiochemically reproducible materials, such as polymer particles, for experimental work.

Acrylates↗

PubMed1976

Synergism of immunogenic and adjuvant-active components of mycobacterial wax D in the induction of adjuvant arthritis.

Two derivatives of wax D, one possessing immunogenicity and the other adjuvant activity, were tested for the possible role in the induction of adjuvant arthritis (AA) in rats. The former, a water-soluble arthritogenic and immunogenic component (WAC), in incomplete Freund's adjuvant, was able to induce delayed hypersensitivity (DH) and mild AA, but failed to function as an adjuvant in rats. The latter, an acetylated wax D (AD) and its subfraction, AD6, did exert adjuvant activity, but were free from immunogenicity and arthritogenicity. The addition of AD or AD6 to the WAC in incomplete Freund's adjuvant, when injected into inguinal lymph nodes, resulted in the production of severe AA with high incidence. Other adjuvants such as pertussis vaccine and lipopolysaccharide could not replace AD6; they failed to enhance AA when combined with the WAC. Also, other mycobacterial antigen, PPD, could not replace wax D-derived WAC; it did not induce AA when coupled with AD6, although it did induce DH to PPD.

Adjuvants, Immunologic↗

PubMed1978

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↗

PubMed1975

Adjuvant activity of mycobacterial fractions. I. Purification and in vivo adjuvant activity of cell wall skeletons of Mycobacterium bovis BCG, Nocardia asteroides 131 and Corynebacterium diphtheriae PW8.

The adjuvant activity of cell wall skeletons (mycolic acid-arabino-galactan-mucopeptide, CWS) prepared from the cells of mycobacteria, nocardia and corynebacteria was examined in vivo in mice and guinea pigs. The cell wall skeletons of Mycobacterium bovis BCG (BCG-CWS), Nocardia asteroides 131 and Corynebacterium diphtheriae PWC suspended in Freund's incomplete adjuvant (FIA) as water-in-oil emulsions showed potent adjuvant activity on the formation of circulating antibody and cell-mediated immunity to bovine serum albumin (BSA), sheep erythrocytes (SRBC) and sulfanylazo-bovine serum albumin (SA-BSA) in mice and guinea pigs. After acetylation or acid treatment, BCG-CWS retained its adjuvant activity, but the activity of BCG-CWS was destroyed completely by alkaline treatment. The cell wall constituents, arabinose-mycolate and arabino-galactan, prepared from BCG-CWS showed no adjuvant activity. It was also shown that BCG-CWS suspended in phosphate buffered saline or associated with oil droplets augmented cell-mediated cytotoxicity in which thymus-derived lymphocytes (T-cells) are effector cells.

Acids↗

PubMedDate not supplied

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↗

PubMed1976

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↗

PubMed1975

Adjuvant effect of Bordetella pertussis vaccine to sheep erythrocytes: enhancement of antibody formation by using subcutaneous administration of adjuvant and antigen.

The subcutaneous route (s.c.) was used to study the adjuvant effect of Bordetella pertussis vaccine (pv) on the primary antibody response to sheep erythrocytes. The reasons for using the s.c. route are discussed. PV, besides enhancing the hemagglutinin response, also markedly increased the number of plaque-forming cells in the draining lymph nodes. A heated preparation of PV was tested and found to possess significant adjuvant activity. Interestingly, the enhancement occurred in the absence of marked enlargement of the lymph nodes, which was characteristic of the unheated preparation. In addition, a crude solubilized cell-free preparation of PV was tested and also found to possess significant adjuvant activity. The activity was only partially abolished by heat. Hence, it was concluded that both heat-labile as well as heat-stable factors contributed to the adjuvanticity of PV. The studies also support the view that the draining lymph nodes represent a principal locus of action of PV and that the s.c. route of administration of adjuvant and antigen provides a suitable model for studying and assaying the adjuvanticity of PV.

Adjuvants, Immunologic↗

PubMed1976

Adjuvant activity of mycobacterial fractions: adjuvant activity of synthetic N-acetylmuramyl-dipeptide and the related compounds.

Immunological activity of synthetic cell wall peptidoglycan subunits was examined in guinea pigs and mice. It was concluded that the minimal adjuvant-active subunit of cell wall peptidoglycan for the induction of delayed-type hypersensitivity to monoazobenzenearsonate-N-acetyl-L-tyrosine and for circulating-antibody formation to bacterial alpha-amylase and the thymus-independent antigen DNP-Ficoll was N-acetylmuramyldipeptide, MurNAc-L-Ala-D-isoGln. N-acetylmuramyldipeptide and 6-O-stearoyl-N-acetylmuramyldipeptide showed no adjuvant activity in the generation of cell-mediated cytotoxic effector cells in the spleens of C57Bl/6J mice after in vivo immunization with the allogeneic antigen mastocytoma P815-X2 cells, but N-acetylmuramyldipeptide showed adjuvant activity after in vitro sensitization of C57Bl/6J mouse spleen cells to the alloantigen mitomycin C-treated DBA/2 mouse spleen cells. It was also shown that 6-O-stearoylation of N-acetylmuramylpeptide could not potentiate the adjuvant activity of N-acetylmuramyldipeptide. Mitogenic and antitumor activities were not observed in either N-acetylmuramyldipeptide or 6-O-stearoyl-N-acetylmuramyldipeptide in mouse systems.

Adjuvants, Immunologic↗

PubMed1979

Liposomes in immunology: impairment of the adjuvant effect of liposomes by incorporation of the adjuvant lysolecithin and the role of macrophages.

The immune response against HSA (human serum albumin) was studied in rabbits after intravenous injection of various HSA preparations. When HSA was injected one day after, together with or coupled to lysolecithin, a late response was found in twelve out of thirteen rabbits, whereas a minority of the rabbits responded when lysolecithin was omitted. These results confirm the adjuvant activity of lysolecithin. A rapid response starting on day 6 was found in rabbits injected with HSA entrapped in liposomes which had been composed of lecithin, phosphatidic acid and cholesterol (PPC liposomes). The response against liposome entrapped HSA was delayed for about one day when the phospholipid adjuvant lysolecithin was incorporated in the liposomes (LPPC liposomes). Results lend support to the hypothesis that the adjuvant activity of lysolecithin and its opposite inhibition of the adjuvant activity of liposomes are mediated by the same mechanism, i.e. inhibition of enzymatic digestion in lysosomes of macrophages.

Adjuvants, Immunologic↗

PubMed1976

[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↗

PubMed1975

The mode of action of immunological adjuvants. II. Generation of a potent precursor of antibody-forming cell by adjuvant.

The mode of action of mycobacterial adjuvants was studied in mice, using a 'plaque size' technique and purified adjuvants, wax D and AD6. Data were obtained which suggest that the adjuvants do not act directly on antibody-forming cells or memory cells but on their precursors. The injection of the adjuvants alone apparently caused the generation of competent precursor cells in the spleen as well as in the bone marrow of mice, which developed large plaques and the generation of memory cells developing large plaques upon antigenic stimulation.

Adjuvants, Immunologic↗

PubMed1975

The mode of action of mycobacterial adjuvants. III. The clonal nature of antibody formation and the effect of mycobacterial adjuvant on antibody-forming cell clones.

Localization of 19S and 7S plaque forming cells detected by Jerne plaque technique were examined in the spleens of irradiated recipient mice transferred with a limiting number of spleen cells and SRBC. All the plaques within a single colony were homogeneous in size and appearance. This supports the clonal nature of antibody formation. An addition of a mycobacterial adjuvant, wax D, to the sensitizing antigen, SRBC, caused an increase in the number of clones (colonies) developing large plaques. It is suggested that there may be normally available competent precursors for clones developing large plaques and the precursors may specifically increase in number in the presence of the adjuvant.

Adjuvants, Immunologic↗

PubMed1977

[Absence of cutaneous phenomena of delayed hypersensitivity in the use of zymosan as adjuvant in comparison with Freund's complete adjuvant in autoimmune experimental orchitis].

In previous researches some of the Authors proved that Zymosan acts as adjuvant in determining the experimental autoimmune aspermatogenesis, in absence of skin reactivity of delayed type. The aim of the present investigations was to ascertain if Zymosan possess some components analogous to those of mycobacteria, which can be considered responsible in determining hypersensitivity reactions of delayed type. The results, obtained also in cross experiments, don't confirm this hypothesis.

Adjuvants, Immunologic↗

PubMed1979

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↗

PubMed1977

Adjuvant effect of Bordetella pertussis vaccine to sheep erythrocytes in mice: enhancement of cell-mediated immunity by subcutaneous administration of adjuvant and antigen.

The subcutaneous route (s.c.) was used to study the adjuvant effect of Bordetella pertussis vaccine (PV) on cell-mediated immunity to sheep erythorcytes (SRBC). The immune response was measured by a sensitive assay procedure in which the antigen is injected intracutaneously into the mouse ear and the inflammatory swelling is measured with calipers. PV significantly enhanced cell-mediated immunity to SRBC, and the enhancement persisted for at least 3 weeks. PV administered up to 6 days before SRBC also significantly enhanced the response; PV injected 1 or more days after SRBC was not effective. In addition, it was found that PV per se released into the suspension medium a cell-free component(s) (pertussis supernatant) that contributed significantly to adjuvanticity. The adjuvanticity of both PV and PS was completely eliminated by heat.

Adjuvants, Immunologic↗

PubMed1978

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↗

PubMed1975

Adjuvant action of capsular polysaccharide of Klebsiella pneumoniae on antibody response. IV. The roles of antigen and adjuvant for induction of primary and secondary antibody responses and for development of immunological memory to bovine serum albumin.

A study was performed to clarify the roles of primary and secondary injections of antigen and adjuvant (capsular polysaccharide of Klebsiella pneumoniae, CPS-K) in induction of antibody responses and in the development of immunological memory in mice to bovine serum albumin (BSA). A primary injection of BSA alone neither induced significant primary antibody response nor increased immunological memory for a secondary antibody response but, if primary injections of BSA and CPS-K were performed simultaneously, high antibody responses were induced. Moreover, a prior injection of BSA alone or CPS-K alone decreased the level of primary antibody response and the degree of increase in memory following the subsequent injection of BSA mixed with CPS-K. In contrast, a secondary injection of BSA alone into mice once primed with a mixture of BSA and CPS-K elicited very high secondary type antibody response and increased secondarily the memory for a tertiary antibody response. Injection of CPS-K simultaneously with or shortly before or after the secondary injection of BSA did not increase the level of the secondary antibody response and the degree of the secondary increase in memory. Augmentation of the secondary antibody response was elicited by simultaneous injection of CPS-K only when the secondary response was induced inadequately by a suboptimum or supraoptimum dose of antigen.

Adjuvants, Immunologic↗