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L Dussourd d'Hinterland

Publications and source records attributed to L Dussourd d'Hinterland.

14 recordsLinked to original sources
PubMed1992

Ribosomes as carriers for antigenic determinants of the surface of micro-organisms.

Over the past twenty-five years, many authors have reported evidence of the immunoprotective capacity of ribosomes isolated from bacteria, fungi and parasites. Since 1971 we have explored the protective capacity of ribosomes isolated from a large variety of micro-organisms responsible for human and animal diseases. Accurate biochemical characterization of ribosomes always reveals trace amounts of non-ribosomal components such as short polysaccharides strongly linked to ribosomal RNA after phenol extraction even under denaturing conditions. rRNA-antigen complexes have been purified from Klebsiella pneumoniae ribosomes inducing high level of protection against homologous experimental infection in mice. Monoclonal antibodies raised against ribosomes and then selected for their ability to confer passive immunity to mice have been used to study the mechanism of the protection induced by ribosomes and to characterize their "immunogenic principle". These investigations have clearly shown the presence on ribosomes of epitopes corresponding to antigens normally exposed on the membrane of the bacteria. In the original concept of "ribosomal immunotherapy" that we have developed, ribosomes can be considered as natural carriers for cell surface epitopes, presenting them to the immune system in a highly immunogenic configuration.

Animals↗
PubMed1991

Bacterial ribosomal immunostimulants prime alveolar macrophages in vivo to produce interleukin 1 in vitro.

Alveolar macrophages (AMs) may play a key role in human respiratory immune defenses, partially by synthesizing and releasing interleukin 1 (IL = 1). D53 (Ribomunyl), a composite bacterial ribosomal immunostimulant, has been recognized as an efficient prevention of respiratory tract infections. In vitro, D53 enhances the IL-1 production by mouse spleen adherent cells. A thymocyte proliferative response assay was used to evaluate the in vitro IL-1 production by AMs in healthy subjects who received D53 immunostimulant. Twelve nonsmoking healthy subjects took part in a prospective double-blind placebo control study. On day 1, a first bronchoalveolar lavage (BAL) was performed to assess IL-1 production by unstimulated and lipopolysaccharide (LPS) stimulated AM. Then, subjects were randomized to receive D53 (n = 6) or its placebo (n = 6) by both oral and subcutaneous injection routes from day 1 to day 15. On day 15, a second BAL was done and AM IL-1 production was again tested. IL-1 production on day 15 did not significantly differ from day 1 in both D53-treated and placebo groups either when AMs were unstimulated or were stimulated with concentrations of LPS resulting in maximal IL-1 production. However, in the D53-treated group, but not in the placebo group, IL-1 production induced by low LPS concentration (5 mg/L) was significantly higher (mean +/- SEM: 1,238 +/- 287 U/10(6) AM) on day 15 in comparison with day 1 (577 +/- 113 U/10(6) AM; p less than 0.05, Wilcoxon W test) and in comparison with the control group (day 15 IL-1 production induced by 5 mg/L LPS, 758 +/- 175 U/10(6) AM; p less than 0.05, Mann-Whitney U test). Moreover, in the D53-treated group, the optimal LPS concentration (ie, LPS concentration that induced maximal IL-1 production) was significantly lower on day 15 (mean +/- SD: 11 +/- 7 mg/L) than on day 1 (16 +/- 7 mg/L; p less than 0.05 Wilcoxon W test). We conclude that D53 immunostimulant in vivo primes AM to produce IL-1 following low LPS concentration stimulation. This may partially explain the protective effect of D53 immunostimulant against respiratory tract infection.

Adjuvants, Immunologic↗
PubMed1989

Phase II study of D.651, an oral vaccine designed to prevent recurrences of vulvovaginal candidiasis.

A vaccine has been prepared with ribosomes of Candida albicans serotypes a and b plus, as adjuvant, membrane proteoglycan from a nonencapsulated Klebsiella pneumoniae. A preliminary phase II trial without placebo control was conducted in 22 women with a history of frequent recurrences of vulvovaginal candidiasis (VVC). Initially, all the patients were treated locally with an antimycotic cream. Beginning at the same time, vaccine was taken orally in capsules containing 0.55 microgram active components. It was administered intermittently over six months, groups of women taking doses of two, three, six or nine capsules. Tolerance was excellent except for mild nausea, probably due to the excipients, in two patients taking nine capsules. Twenty patients completed the study. Only seven of them had a documented recurrence of VVC during the 6 months on vaccine. No recurrence occurred in the eight women taking six or nine capsules per day. Before the study, these 20 patients had had an average of 3.59 attacks of VVC per 6 months. On vaccine, the average rate of recurrence was only 0.55 attacks per 6 months. A multicentre placebo-controlled study of the efficacy of this vaccine is in progress to validate these encouraging preliminary results.

Administration, Oral↗
PubMed1988

Proliferative response of human T lymphocytes to a vaccinal preparation of ribosomes from Streptococcus pyogenes.

The in vitro lymphocyte-activating properties of a ribosomal preparation of Streptococcus pyogenes were investigated. The preparation was mitogenic for human lymphocytes with a peak of 3H-thymidine incorporation occurring after 3-5 days of culture. The response was abolished by removal of CD3-positive cells and by alteration of accessory cells by exposure to L-leucine methyl ester. Most of the cells synthesizing DNA at the end of the culture expressed CD4 or CD8 but not CD20 antigens. No immunoglobulin synthesis was demonstrable. Although the same preparation was shown to be a T-independent polyclonal B-cell activator of murine cells, it preferentially triggers T cells in humans.

Bacterial Vaccines↗
PubMed1987

Polyclonal activation of murine B cells by a membrane proteoglycan of Klebsiella pneumoniae.

The lymphocyte activating properties of a membrane proteoglycan (MPG) extracted from a mutant non-encapsulated strain of Klebsiella pneumoniae (Kp) (biotype a I-145) were investigated. Kp MPG induced a strong proliferative response of BALB/c spleen cells and Peyer's patches cells. Thymidine incorporation was dose-related (from 1 to 100 micrograms Kp MPG/ml) and reached a maximum at day 3. It was not reduced by removal of most adherent cells, nor by depletion of Thy1-2 positive cells, but it was abrogated by removal of surface immunoglobulin bearing cells. Spleen cells from nude mice and those from C3H/Hej mice were strongly stimulated by Kp MPG. Conversely Kp MPG did not induce interleukin 2 production and did not trigger the proliferation of thymocytes but stimulated interleukin 1 production by adherent spleen cells. Finally, unfractionated or B-enriched spleen cells cultured with Kp MPG synthesized IgM and, to a lesser extent, IgG and IgA. It is concluded that Kp MPG is a T-independent polyclonal B cell activator and an inducer of interleukin 1 production.

Animals↗
PubMed1984

Role of the polysaccharide and of the lipopolysaccharide in the immunoprotective capacity of Klebsiella pneumoniae ribosomes.

Ribosomes, ribosomal RNA (r-RNA), capsular polysaccharide (PS-K) and lipopolysaccharide (LPS) were isolated and purified from Klebsiella pneumoniae, type I. The protective capacity of these different fractions was investigated in function of their analytical composition. The results show that ribosomes, and in particular, ribosomal RNA have the greatest protective activity at the lowest concentrations. The role of PS-K in the specific immune response to ribosomes was also investigated. Even at very high levels PS-K failed to afford any significant protection. LPS gave no protection. A stable r-RNA/PS-K complex was isolated by means of affinity chromatography. This complex was uncontaminated by LPS and its existence indicated strong bonding between surface polysaccharide antigens and r-RNA. The r-RNA/PS-K complex was not antigenic in itself but conferred good protection when combined with an adjuvant.

Animals↗
PubMed1980

Ribosomal vaccines: preparation of subcellular fractions.

Methods for isolation and analysis of subcellular bacterial fractions intended to be used in the preparation of ribosomal vaccines are described. Cultivation conditions in fermentors for obtaining maximal growth curve slopes are studied; cultivation is stopped before the end of the exponential growth phase in order to collect biomasses having a high viability rate, which is essential for the quality of the subcellular fractions isolated thereafter. Extraction methods for ribosomes and ribosomal RNA, as well as two proceedings for preparing adjuvant proteoglycans from Klebsiella pneumoniae membranes, are described. The analytical methods used for the control of these preparations and the results obtained for the various fractions are given.

Bacteria↗
PubMed1980

Ribosomal vaccines: immunological study.

Ribosomal vaccines prepared from purified bacterial ribosomes induce the production of specific antibodies in female OF1 mice when administered to the animals both with incomplete Freund's adjuvant or purified Klebsiella pneumoniae cell wall proteoglycans. The study of these fractions concerned purified ribosomes extracted from the following bacteria: Klebsiella pneumoniae, Haemophilius influenzae, Steptococcus pneumoniae, Streptococcus pyogenes A12. Specific antibodies determination by immunoelectro diffusion (IED) and passive hemagglutination (PHA) were used to study the immune response.

Adjuvants, Immunologic↗
PubMed1980

Prevention of bacterial respiratory infection by an association of bacterial ribosomes and membranous proteoglycans. 2. Objective assessment of the response and of the immunological stimulation.

Using a vaccine preparation administered by aerosol for respiratory anti-infectious purposes and corresponding to the original formula of ribosomes and membrane fractions of microbial germs, the authors investigated during a period of nine months whether an objective, transient or lasting stimulation of the total and specific immunoglobulin (Ig) appeared. They provide a statistical analysis based on several serum Ig measurements and demonstrate the stimulant and lasting effect of the vaccine in the production of specific Ig for a sample of patients compared with controls. In those treated they observed apparently disordered variations of the serum levels of the total Ig, which in fact correspond to the initiation of a dynamic equilibrium in relation to the immunogenicity of the vaccine, the initial level of the total Ig and the production of the specific Ig. Finally, after a booster sequence carried out five month after "primary vaccination", they established the restarting of production of specific Ig accompanied this time by a different dynamic response of the total Ig.

Adjuvants, Immunologic↗
PubMed1976

[Sephadex G 100- Separation of the mucicrinic and the mucimitiginic factors from an extract of duodenal mucosa (author's transl)].

The mucicrin stimulating the hexosamine gastrointestinal secretion and extracted form porcine duodenum, was concentrated in the zone 7 using sephadex G 100. The molecular weight of 4000-5000 corresponds to this zone. An opposite activity was detected in zone 3. The factor from digestive mucous origin being able to diminish the hexosamine gastric secretion and not influencing the arterial pressure was called mucimitigin. The molecular weight of about 35000 corresponds to this factor.

Animals↗
PubMedDate not supplied

[Secretory IgA and the antibacterial defenses of the respiratory tract (author's transl)].

The secretory IgA (IgA S) in bronchial mucus is produced by cells which are derived, at least in part, from the BALT (Bronchus Associated Lymphoid Tissue). The physico-chemical characteristics of IgA S (the amino-acid structure of the alpha chain, the secretory component and the J chain) explain three properties of this antibody which enable it to play its part as the first line of defense on the surface of the mucus, namely its resistance to proteolysis, its adherence and its ability to penetrate mucus. The role of IgA S in the antibacterial defense of the respiratory tract has been in doubt for some time because it does not follow the usual processes of antibacterial action, having neither opsonising nor lytic activity. It is thought at present that IgA S exerts its action in an individual way, more directly and peculiar to the secretory immune-apparatus. It acts by 1) causing agglutination of bacteria and by inhibiting their adsorption on the mucous membranes, 2) inhibiting bacterial reproduction and 3) by inactivating bacterial toxins. The combination of these three processes produces a surface defense system which inhibits bacterial penetration of the mucus. Despite the uncertainties which still exist, it is essential that the fundamental immunological data should be included in the complex picture of the mechanisms of defense of the respiratory tract.

Adhesiveness↗