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Biomedical subjects

F Audibert

Publications and source records attributed to F Audibert.

At least 127 records · Page 7Linked to original sources
PubMed1978

Nonspecific immunostimulant activities of synthetic trehalose-6,6'-diesters (lower homologs of cord factor).

Mycobacterial cord factors (6,6'-diesters of trehalose with mycolic acids ranging from C80 to C90) have been shown to protect mice effectively against infection with Klebsiella pneumoniae or with Listeria monocytogenes. Our present findings indicate that the low-molecular-weight cord factor of Corynebacterium diphtheriae (with corynomycolic acids ranging from C28 PTO C36) is equally active. Moreover, its synthetic analog (with synthetic C32 mycolic acid) has the same activity. Two lower synthetic 6,6'-diesters of trehalose with C22 acids, which are described here for the first time, as well as dipalmitate and a dioleate of sucrose, were found inactive. The synthetic C76 trehalose diesters, which are capable of enhancing nonspecific resistance to infection, increase the immune response in mice, even when injected in metabolizable oil. They induce in the injected paws an inflammatory process weaker and more transient than the natural cord factor.

Adjuvants, Immunologic↗
PubMed1978

Absence of binding of MDP, a synthetic immunoadjuvant, to anti-peptidoglycan antibodies.

The binding of the synthetic immunoadjuvant N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP, for muramyl dipeptide) to human and rabbit sera containing peptidoglycan (PG) antibodies was investigated. Studies were performed by employing the corresponding 14C or 125I-labeled compounds in Farr-type binding and inhibition assays. Whereas MDP did not react with naturally occurring or experimentally induced PG-antibodies, the analog of MDP MDP-L-Lys-D-Ala did bind to hyperimmune rabbit anti-PG sera, but not to the human sera tested. These studies indicate that the radioimmunoassays employed basically are applicable for the selection of nonimmumogenic MDP analogs possessing immunoadjuvant activity.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1978

Influence of a synthetic adjuvant (MDP) on qualitative and quantitative changes of serum globulins.

Administered to guinea-pig, a synthetic compound, N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP), has been previously shown to substitute for Mycobacteria in Freund's complete adjuvant. Moreover, MDP increases the humoral immune response even when administered in an aqueous solution to mice. In the present report, it was demonstrated that administered to guinea-pig in a water-in-oil emulsion, MDP or active analogues favoured the production of IgG2 antibodies against ovalbumin. In contrast, derivatives of MDP which had no adjuvant activity failed to induce this particular class of immunoglobulins. MDP without antigen, in contrast with LPS or FCA, did not induce changes in immunoglobulin levels in mice. Administered in mice with an antigen, MDP induces an increase of IgG1 although the immunoglobulin levels are lower than those observed after immunization with adjuvants injected in a water-in-oil emulsion.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1977

Chemically defined bacterial products with immunopotentiating activity.

The adjuvant activity of two chemically well-defined bacterial products is reviewed: (1) lipopolysaccharides of gram-negative bacillis and their acylated detoxified derivatives, and (2) mycobacterial water-soluble fractions and synthetic analogues. Water-soluble adjuvant can substitute for mycobacteria in Freund's adjuvant, but if it is administered in saline, it has little activity. In contrast, lipopolysaccharide under the same conditions markedly increases the humoral antibody response. However, the use of lipopolysaccharide is limited by its toxicity. Water-soluble adjuvant treated with phthalic or succinic anhydride was shown to be an adjuvant when administered in saline. Furthermore, synthetic M-acetyl-muramyl-L-alanyl-D-isoglutamine also increased the humoral immune response when given in aqueous medium instead of in the usual water-in-oil emulsion. This compound, which has a small molecular weight, is not mitogenic, immunogenic, or toxic in mice, and was shown to have adjuvant activity even when given by the oral route.

Adjuvants, Immunologic↗
PubMed1976

Adjuvant disease induced by mycobacteria, determinants of arthritogenicity.

Genetic, endocrine and immunological factors are probably involved in adjuvant polyarthritis. The nature of the vehicle and of the mycobacterial components administered also has a major influence. It was originally assumed that arthritogenicity and adjuvanticity of mycobacterial fractions such as wax D were intimately related. Our previous findings showed that the water soluble adjuvant (WSA) of M.smegmatis which could substitute for mycobacterial cells in Freund's complete adjuvant and induce delayed hypersensitivity was not arthritogenic in the Wistar rat. We have since observed that auto-immune diseases could be elicited by WSA. Therefore experiments were repeated using the very susceptible Lewis strain. The activity of cord factor and of various mycobacterial preparations suspended in mineral or in peanut oil was also evaluated in mice and in normal or hypophysectomized rats. Our present findings confirm the absence of arthritogenicity of WSA in the Lewis strain. They also indicate that cord factor with WSA does not suffice to induce a generalized adjuvant disease, but that a mycobacterial component which could be susceptible to lysozyme treatment is required also. However, the local inflammation of the injected limb was produced by a preparation of cord factor administered in mineral or even in peanut oil. This was observed in normal or hypophysectomized rats and in Swiss mice which were not susceptible to the generalized disease.

Animals↗
PubMed1976

Modulation of the immune response by a synthetic adjuvant and analogs.

N-Acetylmuramyl-L-alanyl-D-isoglutamine increases the humoral immune response of mice when given in aqueous media instead of the usual water-in-oil emulsions. Moreover, this compound is adjuvant active even by the oral route. In view of studying the relation between chemical structure and biological activity, several synthetic analogs were tested. The immune response could be modulated according to chemical modifications, and the synthetic analog with D- in place of L-alanine was shown to inhibit the immune response.

Adjuvants, Immunologic↗
PubMed1976

Activity in saline of phthalylated or succinylated derivatives of mycobacterial water-soluble adjuvant.

A water-soluble fraction (WSA) of the cell wall can substitute for mycobacterial cells in Freund complete adjuvant. However, when WSA is administered in saline instead of in a water-in-oil emulsion, its adjuvant activity is very weak, and under certain experimental conditions it can even inhibit the humoral immune response. The data reported in the present study show that after treatment by phthalic or succinic anhydride the adjuvant activity of WSA was markedly changed, since high levels of circulating antibodies were produced when these derivatives were administered with an antigen in an aqueous medium. Moreover, the antigenic determinants of WSA were modified and acylated WSA had no tuberculin-like activity.

Acylation↗
PubMed1976

Cell suppression in PPD-induced blast specific response of human peripheral blood lymphocytes.

Secific stimulation of T-cells by PPD was inhibited by their autologous B cells. This inhibition was obtained with B cells separated either by depletion of E-RFC or by elution, with human IgG of lymphocytes bound to Sephadex beads coated with rabbit antibodies anti-human Fab fragments. The suppression was proportional to the number of B cells added to 10(6) T cells incubated with PPD and as previously reported was more marked in the case of B or T cells from BCG-vaccinated subjects with negative skin tests. The suppressive phenomenon required viable B cells and was inhibited by cycloheximide but was not altered by pretreatment of suppressor cells with actinomycin D or colchicine. It seems that B-suppressor cells interfere with recognition of PPD by T cells rather than with the proliferative phase of the specific blast response. Using various surface markers (i.e. Ig, C3 and Fc receptors) it was shown that the suppressor cells represent a subset of Ig-bearing B cells which do not carry Fc receptors.

Antigens↗
PubMed1975

[Increase of immune response by administration of metabolizable vegetable oil emulsions].

Though highly efficient, Freund's adjuvant has serious limitations because it contains mineral oil and isomannide monooleate emulsifier (arlacel A). The present study describes the conditions under which a stable water in oil emulsion can be produced by using metabolizable peanut oil with arlacel. When mycobacteria are added, a potent emulsified oil adjuvant is obtained which increases the immune response to BSA and to influenza vaccine.

Adjuvants, Immunologic↗
PubMed1975

[Adjuvant and mitogenic effects of detoxified lipopolysaccharides].

McIntire and al. have observed that a lipopolysaccharide (LPS) extracted from E. coli could be detoxified by succinylation or phtalylation and remained capable of enhancing the immune respose to serum albumins. The data reported here confirm that several LPS preparations after treatment by phtalylation retained their adjuvant activity when injected with bovine serum albumin or influenza vaccine. Yet their toxicity (as measured in adrenalectomized mice) was at least 10 000-fold smaller. Furthermore it was observed that after phtalylation LPS could still induce blastic transformation of murine B-derived lymphocytes. Thus it was possible to dissociate the toxicity of LPS from both its adjuvant and mitogentic activities.

Adjuvants, Immunologic↗
PubMed1975

Biological activities of endotoxins detoxified by alkylation.

It has been previously observed that lipopolysaccharides can be detoxified by alkylation and yet retain their adjuvant activity. Our present findings confirm these results and show, moreover, that these derivatives did not lose their capacity to protect mice against lethal irradiation and lost only partially their ability to interrupt pregnancy or to induce blast transformation of murine B-lymphocytes. However, in contrast with lipopolysaccharides, these alkylated preparations did not enhance the nonspecific resistance of mice to a bacterial infection. The various bilogical functions of endotoxins can therefore be separated and are not uniformly related to their toxicity.

Abortion, Spontaneous↗