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Biomedical subjects

G Normier

Publications and source records attributed to G Normier.

36 records · Page 2Linked 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↗
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↗
PubMed1989

Relationship between bacteria and IgE.

In this preliminary report, we describe our inability to induce IgE antibody to a well-characterized bacterial component, the membrane proteoglycan of Klebsiella pneumoniae and its major protein fraction FIII-B in BALB/c mice. In contrast, an immunomodulatory effect of membrane proteoglycan of K. pneumoniae on the IgE and IgG antibody responses to ovalbumin could be demonstrated.

Allergens↗
PubMed1988

Induction of murine B cell proliferation and immunoglobulin synthesis by some bacterial ribosomes.

Ribosomal preparations from Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, and Streptococcus pneumoniae were investigated with respect to their activating capacity towards murine lymphoid cells. The proliferation of BALB/c spleen cells was induced in a dose-dependent fashion (from 1 to 100 micrograms/ml) by ribosomes of K. pneumoniae, H. influenzae, and S. pyogenes with a peak activity at 48 or 72 hr of culture. The majority of the blast cells induced by these ribosomal preparations were positive for surface-immunoglobulin (S-Ig) and negative for Thy 1.2. Furthermore, K. pneumoniae, H. influenzae, and S. pyogenes ribosomes induced the synthesis of IgM and some IgA. Cell proliferation and induction of IgM production were also demonstrated with the 3 ribosomal preparations using spleen cells from athymic nude (nu+/nu+) mice, Lyb-5-defective CBA/N spleen cells, B cell-enriched and T cell-depleted BALB/c spleen cell suspensions, as well as spleen cells from the Ips gene-deficient C3H/HeJ strain. Cell culture supernatants contained specific anti-ribosome IgM antibodies. Antibodies of other specificities (anti-sheep erythrocytes) were also demonstrated in supernatants from K. pneumoniae-stimulated cultures. Evidence against a possible role of contamination of K. pneumoniae and H. influenzae ribosomes by lipopolysaccharide- or lipid A-associated proteins in this effect is discussed. Ribosomes from S. pneumoniae did not induce 3H-thymidine incorporation nor Ig production. None of the 4 ribosomal preparations was found to stimulate T cell blastogenesis or to induce interleukin-2 production by naive BALB/c spleen cells. Finally, ribosomes from H. influenzae, S. pyogenes, S. pneumoniae but not those of K. pneumoniae stimulated interleukin-1 production by adherent spleen cells, from BALB/c mice.

Animals↗
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↗
PubMed1985

NK-cell stimulating properties of a membrane proteoglycane from non-capsulated Klebsiella pneumoniae biotype a.

Upon testing the individual fractions of a composite bacterial vaccine for biological activities, a potent immuno-stimulatory capacity could be demonstrated within a crude membrane proteoglycan preparation from Klebsiella pneumoniae. One of its characteristic features was the capacity to induce alpha-type interferon and increased NK activity in vivo in mice, following intraperitoneal or oral administration. A highly purified fraction from the crude preparation was obtained using alkaline hydrolysis, delipidation and size fractionation. This fraction was shown to be a very potent inducer of NK cells in vivo or in vitro, where in the latter systems concentrations as low as 0.1 microgramme per ml were highly efficient.

Adjuvants, Immunologic↗
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↗
PubMed1982

Study of the mode of action of ribosomal vaccines from Klebsiella and Streptococcus pneumoniae and their ribonucleic and protein fractions using passive immunization.

The vaccinating potency of ribosomal fractions of Klebsiella pneumoniae and Streptococcus pneumoniae as well as their ribosomal RNA and protein fractions has been studied with respect to their ability to induce cellular or humoral immunity. Experiments with transfer of serum or spleen cells from vaccinated animals have shown that anti-Klebsiella immunity is essentially cellular, while streptococcal immunity is exclusively humoral. Results have been discussed as a function of differential results for the various fractions under study.

Animals↗
PubMed1982

An attempt to localize the vaccinating power of Klebsiella pneumoniae ribosomal preparations using saccharose-gradient ultracentrifugation.

The study of the vaccinating power of ribosomal vaccines against Klebsiella pneumoniae led us to define the chemical nature which supports this protective activity. We tried to separate this support and the ribosomes by sucrose gradient ultracentrifugation. We isolated high protective membrane vesicles by this technique applied to salt-washed ribosomal preparations. When the ribosomal preparations were exposed to SDS, the protective activity was conserved all along the gradient, with no correlation with the ribosome concentration. The addition of bovine serum albumin to the ribosomal preparation focused the protective activity on the ribosomal peak. No correlation was observed between the response to capsular polysaccharide and the vaccinating power of the fractions.

Ammonium Chloride↗
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↗
PubMed1979

Role of interferon in mice in protection against influenza A virus by bacterial ribosomes together with membranal glycoproteins of Klebsiella pneumoniae as adjuvant.

Nonspecific protection against infectious aerosols of influenza A virus was obtained in Swiss mice after vaccination by aerosols of bacterial ribosomes together with membranal glycoproteins extracted from Klebsiella pneumoniae as the adjuvant. It was shown that repeated stimulant aerosols were necessary to obtain this protection. Routine estimation of serum interferon levels after administration of the association of ribosomes plus membranal glycoproteins to the animals by aerosol or intravenous route showed that there was no correlation between protection and the presence of serum interferon. It was shown that the serum interferon-inducer activity was due to ribosomes. No induction of serum interferon was obtained with membranal glycoproteins used separately. Local liberation of interferon in the mucous membrane of the upper respiratory tract was not investigated.

Adjuvants, Immunologic↗
PubMed1978

Immuno-stimulation by a ribosomal vaccine associated with a bacterial cell wall adjuvant in humans.

We have studied a new vaccine of ribosomal nature associated with glycoprotein cell walls from Klebsiella pneumoniae which served as an immunoadjuvant. Thus vaccine was administered by the aerosol route to working men free of any important disease, especially of respiratory disease. A total of 104 men working for the Commissariat à l'Energie Atomique, all volunteers, were randomly placed into two groups. During the first period, 51 patients (group I) were vaccinated three times a week during 5 weeks, and the second group was used as control. During the second period, which started on day 225, the control group received the vaccine, and the first group was revaccinated. Results of this experience show a significant difference in the immunity of the two groups. The specific antibodies increased with vaccination as illustrated by chi-square test (Yates correction), which corresponds to an independent probability equal to 0 (P = 0.5 X 10-4).

Adjuvants, Immunologic↗
PubMedDate not supplied

Binding to leukocytes and induction of TNF alpha production involve different sites within the lipid-A region of LPS-like molecules.

The induction of TNF alpha synthesis in whole blood culture assay and isolated peripheral blood mononuclear cells was investigated, using LPS from Klebsiella pneumoniae and two water-soluble 34 kDa derivatives designed as acylpolygalactoside (APG) and EFA-APG, an APG molecule bearing two additional ester-linked fatty acids. Both APG and EFA-APG bind to monocytes by specific ligand receptor interaction but only EFA-APG could induce TNF alpha synthesis. It is concluded that ester-linked fatty acids are not involved in LPS binding to the cell surface, but play a critical role in the triggering of cellular responses.

Carbohydrate Sequence↗
PubMedDate not supplied

[Experimental infection by "Salmonella typhi-murium": protective role of homologous ribosomal extracts in calves (author's transl)].

Eleven calves, 6 months old, vaccinated or not, have been infected experimentally with 10(7) Salmonella typhi-murium, administered by oral route. The control calves had a serious illness, characterized by a severe diarrhoea, hepatic and renal symptoms and a heavy infestation of the main organs. The other five calves, which were orally and subcutaneously vaccinated with ribosomal extracts of S. typhi-murium and S. dublin showed only a moderate alteration of their health while biochemical disorders at the level of liver and kidneys disappeared. However, salmonella were found in mesenteric lymph nodes, but in much lower amounts than in controls.

Animals↗