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P H Lagrange

Publications and source records attributed to P H Lagrange.

At least 145 records · Page 8Linked to original sources
PubMedDate not supplied

Viability, heat stability and immunogenicity of four BCG vaccines prepared from four different BCG strains.

Four BCG strains, French 1173-P2, Danish 1331, Japanese 172 and Glaxo-1077, among those most widely used throughout the world for tuberculosis vaccination, were prepared according to the respective conditions in each BCG-production unit. These 16 vaccine preparations were distributed and compared using standardized in vitro and in vivo conditions, based on optical density and bacillary mass/ml. The results presented in this report concern only the 4 freeze-dried BCG strains prepared by the Institut Pasteur BCG unit. It is shown that these 4 preparations differ in their in vitro characteristics such as growth, morphology, heat stability and viability, tested by colony-forming units and the ATP content. In addition, statistically significant differences were observed in biological control tests performed in guinea-pigs and mice when they were immunized with the same concentrations of 4 reconstituted vaccines. For instance, in tests measuring hallmarks of cell-mediated immunity--such as local granuloma formation, spleen index, delayed-type hypersensitivity to tuberculin, and non-specific immunopotentiation to unrelated antigen--a ranking order of relative immunopotency of the four strains was made, giving the following classification in decreasing order: French 1173-P2, Danish 1331, Japanese 172 and Glaxo-1077. Specific acquired resistance after BCG vaccination in mice was obtained with all four vaccines. However, higher protection was observed in mice vaccinated with Glaxo-1077 and French 1173-P2 strains. No obvious correlation existed between the intensity of cellular post-vaccination resistance and the above CMI tests, except those concerning the three-week index of BCG infection measured in the spleen, which correlated with the protection test.

Adenosine Triphosphate↗
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Natural resistance to mycobacteria: antimicrobial activity and reactive oxygen intermediate releasing functions of murine macrophages.

After infection with Mycobacterium lepraemurium or with M. bovis strain BCG (bacillus Calmette-Guérin), splenic macrophages from mice naturally resistant (NR) to these pathogens (C3H and A/J) spontaneously produced H2O2, whereas splenic macrophages from naturally susceptible (NS) mice (C57BL/6 and Swiss) did not. None of them produced superoxide anion O2-. In addition, NR macrophages had higher levels of superoxide dismutase (SOD) than did NS macrophages. In vivo treatments thought to enhance H2O2 metabolism (phorbol myristate acetate, SOD, Zymosan) decreased M. lepraemurium survival, whereas treatment with diethyl-dithiocarbamate, a potent inhibitor of SOD, had the converse effect. These results favour the hypothesis of a link between natural resistance to BCG (and M. lepraemurium) and H2O2 metabolism, with higher producers being naturally resistant.

Animals↗
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Role of T lymphocytes in the resistance and immunopathology of experimental Chagas' disease. I. Histopathological studies.

The results reported here show that Trypanosoma cruzi can parasitize almost all tissues of mice; however, the T-dependent immune response controls parasite invasion, leading undesirable immunopathological effects. Inflammatory infiltrate was rare in heart or skeletal muscle and other organs of Nu/Nu, but was abundant in tissues of Nu/+ mice. Cellular inflammatory lesions could be induced in Nude mice by the transfer of lymph node cells from Nu/+ animals infected with T. cruzi.

Adrenal Glands↗
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Time course and histological differences between sheep red blood cells and tuberculin DTH reactions in mice.

Delayed-type hypersensitivity (DTH) reactions induced with sheep red blood cells (1 X 10(8) SRBC/mouse) or with attenuated viable Mycobacterium bovis (4 X 10(6) BCG/mouse) inoculated subcutaneously and elicited, respectively, with SRBC or protein-purified derivative (PPD), were studied regularly in separate groups of outbred mice and compared during a period of one year following immunization. The present report shows the existence of two distinct types of DTH reactions. The SRBC type consists of a reaction which peaks consistently at 18 h, reaches a maximum 4 days after immunization, and decreases progressively until the fourth month. This local reaction, mediated by specific committed T cells as demonstrated by adoptive transfer experiments, was shown to consist mainly of a polymorphonuclear leukocyte infiltration. The PPD type consists of a local reaction which presents a different time course, the peak shifting from 18 to 42 h during the first two months after immunization, and which persists unchanged over a year after immunization. This second type of DTH reaction consisted of an early phase of polymorphonuclear infiltration followed by an increased number of mononuclear cells. Evidence is also given that the differences in the expression of these two types of DTH reactions depended neither upon the physical characteristics of the two antigens used for elicitation nor upon the nonspecific environmental modulating activity of BCG, since soluble SRBC protein and heat-killed BCG cells elicited the same distinct types, and the two distinct DTH reaction types could be elicited in mice immunized with both BCG and SRBC.

Animals↗
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Dissociation between cell-mediated immunity and acquired resistance in systemic murine candidiasis.

Mice immunized with 10(7) heat-killed (HK) Candida albicans injected subcutaneously with or without BCG, used as an immunoadjuvant, were able to develop strong significant delayed-type hypersensitivity (DTH) against C. albicans but without any increase in specific resistance, as measured by median survival time and enumeration of yeasts inside target organ such as lungs, liver, spleen and kidneys after an intravenous (i. v.) challenge of 1 X 10(6) live C. albicans. Concomitant activation of the mononuclear phagocytic system, measured in vivo by increased resistance to L. monocytogenes, was shown to be induced in immune mice challenged i. v. with 1 X 10(6) HK C. albicans. These results are in favour of a clear distinction between DTH and acquired resistance to systemic candidiasis, even in the presence of specific activation of macrophages.

Animals↗
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Vaccines against mycobacteria and other intracellular multiplying bacteria.

As the prototype of a vaccine against mycobacterial infection, the BCG (bacille bilié Calmette et Guérin) has been used against tuberculosis for more than 60 years. It is the only live attenuated vaccine used on humans in more than 182 countries or territories in the world, and very few changes have been made in its fabrication and distribution, except for the production of lyophilized seed-lots. However, its history is marked with controversies concerning its innocuity and efficacy. While BCG safety is no longer a matter of debate, the question of its effectiveness is still pertinent, and results in several controlled trials have shown great variability (from 0 to 80%). The studies of different variables involved in such results have shown statistical bias, and numerous factors are involved in the highly complex interrelationships between the host, the pathogen and environmental factors. World-wide research is now being conducted under the auspices of the World Health Organisation, in order to gain further knowledge of the immunology of tuberculosis and leprosy. Such results are aimed at understanding variations in BCG efficacy and producing strategies for developing new vaccines and alternative methods for prophylaxis and diagnosis. Concerning human infections due to other facultative intracellular multiplying bacteria, there are relatively few vaccines which are able to give long-lasting and efficient protection. Some controversy remains as to the live attenuated mutant GalE S. typhi Ty21a, and there is hope for the new insoluble phenol extract from Brucella abortis, strain B19. Further research is necessary on the others, for instance, Listeria monocytogenes, Chlamydia trachomatis and Legionella sp.

Bacterial Infections↗
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The immunology of leprosy: speculations on the leprosy spectrum.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. The disease presents a wide spectrum of clinical manifestations, ranging from lepromatous to tuberculoid leprosy; each form may be punctuated by episodes of acute exacerbation, called reactional states. These polar forms and reactional states appear to be determined by immunologic interactions between the host and the microorganism. This review describes the different measurable parameters that permit the classification of a particular form according to clinical, bacteriologic, histologic, and immunologic spectra. Secondly, the current state of knowledge on essential immunologic features of leprosy is presented, with a description of the various alterations of cellular and humoral immune responses that can be tested by specific and nonspecific methods. The last part of the review is devoted to an analysis of the leprosy spectrum and to speculations about a number of possible factors that may influence the immune response of the host in a manner analogous to that observed in experimental models.

Animals↗
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An evaluation of the polymerase chain reaction amplicor Chlamydia trachomatis in male urine and female urogenital specimens.

BACKGROUND AND OBJECTIVES: The new commercially available polymerase chain reaction (PCR)-based assay, Amplicor C. trachomatis, was compared with cell culture of C. trachomatis, for the detection of chlamydial urogenital infections. GOAL OF THIS STUDY: To evaluate whether the Amplicor C. trachomatis PCR could improve the diagnosis of chlamydial urogenital infections, compared with cell culture of C. trachomatis considered as the reference method. STUDY DESIGN: A total of 466 men and 290 women attending a sexually transmitted disease (STD) clinic were tested by the Amplicor test in urine in men, and in the cervix and urethra in women, and by cell culture in the urethra of both men and women and in the cervix of the women. RESULTS: The prevalence of C. trachomatis was 13.7% by cell culture and 14.4% by the Amplicor test in men, and 3.5% by cell culture and 4.5% by the Amplicor test in women. After resolution of the discrepant results, the sensitivity of culture was 91.4% in male urethral specimens and 83.3% in endocervical and female urethral specimens. The resolved sensitivity of the PCR assay was 92.7% in male urine, 91.7% in endocervical samples, and reached 100% in testing both endocervical and female urethral specimens. CONCLUSION: This rapid PCR-based assay showed an improvement in quality for diagnosing C. trachomatis infections.

Adolescent↗
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[The association of cryptosporidiosis and isosporosis in a patient with acquired immunodeficiency syndrome (AIDS)].

We describe one case of AIDS patient who have excreted simultaneously oocysts of Isospora belli and Cryptosporidium species for ten months. These parasites were noticed with qualitative and quantitative changes. Different treatments were successless about these parasites. This double infestation in tropical AIDS patients appear to have a conspicuously frequency.

Acquired Immunodeficiency Syndrome↗
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[Delayed local reaction (DLR) after BCG vaccination in mice. I.--Description (author's transl].

Mice injected subcutaneously in the hind footpad with BCG vaccine subsequently develop a local reaction. This local reaction could be divided into three stages: a first characterized as an acute inflammatory reaction, a second as an active granulome formation, and a third as a chronic long lasting inflammatory reaction. The second stage is mainly formed by the appearance of a typical histiolymphocytic granuloma. The intensity of the delayed local reaction (DLR) is measured by the swelling of the injected footpad. This reaction does not occur after injection with irradiated (gamma or UV) BCG in normal mice, nor after injection of living BCG in Nude mice, indicating a T-cell immune response which develops during the in vivo multiplication of this intracellular bacteria. When the lymphoproliferation response in draining node was measured, a direct correlation was found with the intensity of the DLR, and the 125IUdR incorporation into DNA after injection of living BCG or after an irradiated BCG inoculation. The intensity and the rapidity of the onset of this DLR depend upon the dose of viable BCG inoculated in the mouse. When the DLR reached its peak, a linear dose relationship was observed in C57Bl/6 and in NCS mice.

Animals↗
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[Delayed type hypersensitivity reactions to "Candida albicans" in mice (author's transl)].

Mice injected intravenously (IV) or subcutaneously (SC) with living Candida albicans developed subsequently delayed-type hypersensitivity (DTH) which was measured in vivo by the footpad test after injection of 10(6) heat killed C. albicans (HKC.a.). Compared to systemic injections, SC immunizations with living C.a. gave higher levels of DTH, and lethality was absent. Subcutaneous injections of hundred time more doses of HKC.a. were also able to produce in normal mice a DTH reaction elicited with HKC.a. or with C.a. soluble extracts, but not with candidine. Intraperitoneal injections of varying doses of HKC.a. or subcutaneous injections of varying doses of C.a. soluble extracts failed to produce significant DTH. High levels of sensitization can be induced by using cyclophosphamide or BCG or both pretreatment before immunization, which seems to indicate immunomodulating factors for induction or expression of DTH in normal mice after injections of HKC.a. Kinetics of the local reaction elicited with HKC.a. fulfull usual criteria of DTH in actively immunized mice after CY pretreatment or not, and in passively immunized mice after systemic or local transfer of spleen cells from actively immune donors. Serum from same group of donors was unable to transfer DTH.

Animals↗
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[Effect of bacterial phospholipidic extract (EBP) on the immune response in mice toward sheep red blood cells (author's transl)].

Injection in mice of bacterial phospholipidic extract (EBP) stimulates immune responses to sheep red blood cells (SRBC). Immunostimulation was observed mostly for antibody response and to a less extent for delayed-type hypersensitivity (DTH). The adjuvant effect of EBP is dependent on several factors: dose, route and time. Maximal activity was found when mice received 100 to 200 microgram of an intravenous injection of EBP, twenty-four hours before systemic immunization with optimal doses for antibody or DTH response. Subcutaneous injection of EBP did not modify the cellular or humoral immune response to SRBC inoculated subcutaneously in the same or in a different site of EBP. Adjuvant action of EBP was different of those of endotoxin, since the later suppresses the DTH response to optimal dose of SRBC, this effect being abolished with cyclophosphamide pretreatment. EBP inoculated intravenously suppressed the local reaction of a DTH adoptively transferred with immune spleen cells. These results taking together seem to indicate a preferential role of EBP on the accessory cells in the induction or expression of the immune response to SRBC.

Adjuvants, Immunologic↗
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[Inflammation and resistance of mice infected by "Candida albicans" (author's transl)].

An inflammatory reaction induced by the subcutaneous injection of talc embedded in a gel calcium phosphate increased resistance of mice challenged intravenously with Candida albicans. The relationship between the absolute number of polymorphonuclear phagocytes in the blood and this protective effect seems to indicate a major role of polymorphonuclear leukocytes following inflammation.

Animals↗
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The influence of BCG vaccination on murine leprosy in C57BL/6 and C3H mice.

Cross-reactivity between Mycobacterium lepraemurium (MLM) and BCG vaccine was found and evaluated in vivo, in C57BL/6 mice, in terms of delayed-type hypersensitivity, local granulomatous response at the injected site and limitation of growth of the challenge inoculum in the draining node. Cross-reactive specific protection and local reactivities were transferred in syngeneic normal recipients by means of non-adherent lymphoid cells from immune donors. When BCG vaccine was injected either intravenously or subcutaneously in C57BL/6 and in C3H mice, it was able to induce resistance to local infection with living MLM in both strains, but no alteration of the local granulomatous reaction (equivalent to local specific immune response) was observed in C3H mice, as compared to the control. When mice were immunized with one or two injections of heat-killed MLM after the immunomodulating effect of BCG vaccination, better immunization was not achieved. In order to test the presence of strain-related immunosuppressive mechanisms, mice were cyclophosphamide-treated during the immunization process. As expected, higher specific DTH reactions were obtained in both strains, but with only a slight increase of the protective mechanism. Protection was always higher in C57BL/6 than in C3H mice. The specific and non-specific immune responses to BCG vaccine were then evaluated in both strains with different parameters: in vivo lymphoproliferative response in the draining node, delayed local granulomatous reaction at the injected site after a subcutaneous injection, increase in spleen index, kinetics of the immunopotentiation to a thymus-dependent antigen (sheep red blood cells) after a single intravenous injection of BCG. A striking interstrain difference was observed; C57BL/6 mice were able to mount a more rapid and marked immune response as compared to C3H mice (which only developed a delayed and slight response). Moreover, these differences were associated with the fact that BCG did not seem to multiply properly in C3H mice during the first two weeks after inoculation. Thus, it was concluded that higher natural resistance to pathogens and cross-reactive preimmunization with related microorganisms can interfere with the artificial immunization when living microorganisms are used. Implication for vaccination to mycobacterial infection (tuberculosis and leprosy) are discussed.

Animals↗
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Comparative studies of different strains of BCG vaccine in mice: T-cell dependent immune responses.

Three tests have been selected to demonstrate the close relationship between the innate immunogenicity and immunopotentiating capacity of different strains of BCG vaccines grown under the same conditions. The five strains of BCG which have been most extensively studied were PASTEUR, PHIPPS, TICE, CONNAUGHT and GLAXO. The first four are alike, they have similar growth characteristics and closely resemble each other, in immunological properties-lymphoproliferative response in vivo and T-cell potentiating effect-PASTEUR BCG being the strongest. GLAXO strain is different in these respects and is shown to have atypical properties.

Animals↗