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Biomedical subjects

O Garraud

Publications and source records attributed to O Garraud.

At least 55 records · Page 3Linked to original sources

Assays for adjuvanticity of new formulations and of carrier proteins for inducing antibody responses to selected immunogens in the squirrel monkey Saimiri sciureus.

Different ways to improve antibody (Ab) responses following immunizations with selected antigens (TT and HSVgD) were investigated, and thus new adjuvant formulations and carrier molecules in a non-human primate experimental host, the squirrel monkey Saimiri sciureus, were assayed. Both quantitative and qualitative humoral responses were determined by means of radio-immunoassays using monoclonal Ab directed at Saimiri IgG. First, the adjuvanticity of the Syntex (SAF-1) adjuvant and of five new adjuvant formulations were assessed towards the selected Ag. This indicated that all the adjuvants induced similar antigen-specific Ab responses, although the adjuvants could modify to some extent the pattern of the qualitative Ab response. Second, we evaluated an adjuvant-free vaccine approach using a synthetic Ag from the circumsporozoite protein of Plasmodium falciparum as immunogen, this Ag being coupled to purified protein derivative (PPD) or to a recombinant heat shock protein from Mycobacterium tuberculosis. These constructs led to good antibody responses as well as an excellent memory effect. Bacille Calmette-Guérin (BCG) priming was required in conjunction with PPD as a carrier molecule to allow homogeneous Ab responses, whereas the heat shock protein construct gave a less homogeneous Ab response regardless of whether a BCG priming was done. We, in addition, discuss the relevance of Saimiri monkeys as experimental models for studies directed at evaluating the immunogenicity of further vaccine candidates.

Adjuvants, Immunologic↗

Comparison of the effects of adjuvants and adjuvant doses on the quantitative and qualitative antibody response to selected antigens in New World squirrel monkeys Saimiri sciureus.

The effect of several adjuvants and of adjuvant doses on the quantitative and qualitative antibody response to tetanus toxoid (TT) and a recombinant herpes simplex virus peptide (HSVgD) was evaluated in the New World monkey Saimiri sciureus. All adjuvant formulations were effective in inducing a strong antibody response to these antigens. The qualitative antibody response, as defined by monoclonal antibodies 3A2/G6 and 4G3/B5, was determined. Only 3A2/G6+ antibodies were induced after immunization with HSVgD irrespective of the adjuvant used and after immunization with TT alone. However, both types of antibodies were induced against TT in the presence of the adjuvants tested. These data suggest that both adjuvant and antigens can intervene in driving the quality of the antibody response induced after immunization. Strong antibody response to TT was induced at any adjuvant dose tested, suggesting that lower doses are as effective as higher doses. These findings can have implications on the design of future trials of vaccine candidate constructs in monkeys and eventually in human beings.

Adjuvants, Immunologic↗

Fc gamma R-expressing monocytes are necessary for PWM-induced proliferation of Saimiri sciureus peripheral blood mononuclear cells.

When used as a polyclonal activator of blood immunocompetent cells in the squirrel monkey, pokeweed mitogen (PWM) failed to induce lymphoproliferation unless either autologous or human serum was added to the culture medium, instead of a serum assumed to be deprived of Ig such as foetal bovine serum. We thus attempted to delineate activation processes initiated by PWM and which required both monocytes and native Ig molecules. For instance, the physical presence of live monocytes within lymphocyte suspensions vs. paraformaldehyde-fixed monocytes or products of monocytic origin was an absolute prerequisite for inducing squirrel monkey lymphocytes to proliferate in the presence of PWM. In addition, a combination of monocytes and native Ig were further shown to induce lymphocytes to proliferate in the presence of PWM. We therefore questioned whether Fc gamma R on the surface of monocytes vs. Fc gamma R expressed by other cells were involved in the initiation of PWM-driven lymphoproliferation. PWM may represent a useful tool for studies of Fc gamma R-mediated immunological processes.

Animals↗

Successful primate immunization with peptides conjugated to purified protein derivative or mycobacterial heat shock proteins in the absence of adjuvants.

We have previously shown in mice that antibodies can be induced to synthetic malaria peptides conjugated to mycobacterial antigens, such as purified protein derivative (PPD) or heat shock proteins (hsp), and given in the absence of adjuvants after a previous priming with bacille Calmette-Guérin (BCG). In the present study we investigated this model of immunization in the non-human primates, Saimiri sciureus monkeys. Monkeys primed with BCG subcutaneously and then immunized subcutaneously with the Plasmodium falciparum sporozoite (NANP)40 synthetic peptide conjugated to PPD or mycobacterial hsp of 65 or 70 kD, in the absence of adjuvants, produced antipeptide and anti-sporozoite IgG antibodies. Interestingly, the carrier effect of the hsp of 70 kD for the induction of anti-(NANP)40 antibodies was also observed in the absence of a previous priming with BCG. These data suggest that such a vaccination strategy may be applied to humans.

Adjuvants, Immunologic↗

Changing patterns of the IL-2/IL-2R pathway of lymphocyte activation following exposure to Plasmodium falciparum products: a study with squirrel monkey peripheral blood mononuclear cells.

Squirrel monkeys are experimental hosts useful for studies on human malaria. In the present work, in vitro lymphocyte reactivity was measured by proliferation in the presence of Plasmodium falciparum-derived products, and found to depend on the previous malarial status of the animals and upon the source and/or the nature of the P. falciparum-derived material. Special attention was given to the IL-2/IL-2R pathway of lymphocyte activation. Culture supernatant from P. falciparum-parasitized erythrocytes exerted an inhibitory effect towards T lymphocytes obtained from P. falciparum-non-immune squirrel monkeys, when activated, for instance, by PHA. These lymphocytes did not incorporate tritiated thymidine (neither they did proliferate) although they expressed IL-2 alpha and beta binding chains and secreted IL-2 (or at least TCGF). This inhibitory effect could not be rescued by the addition of rhIL-2, although the assayed lymphocytes could retain the ability to continue their cell cycle progression and divide after removal of the P. falciparum-derived inhibitory product(s). The incidence of anti-mitogenic molecules which impair the IL-2/IL-2R pathway of lymphocyte activation in malaria related processes is discussed.

Animals↗

Functional characterization of the antibody-mediated protection against blood stages of Plasmodium falciparum in the monkey Saimiri sciureus.

The squirrel monkey Saimiri sciureus is one of the World Health Organization recommended experimental models of Plasmodium falciparum blood stage infection. Anti-malaria antibodies developed by this host after a drug-controlled infection play an important part in the acquired protection against the P. falciparum blood stages. Furthermore, the use of two anti-Saimiri immunoglobulin (Ig) monoclonal antibodies (mAb) has permitted the differentiation between protective (mAb 3A2/G6) and non-protective (mAb 3E4/H8) antibodies, as shown by transfer experiments to recipient monkeys infected with blood stage parasites. In the present study we have established that protection conferred by the 3A2/G6+ protective Ig preparation is strictly associated with an in vitro opsonic activity. Such an opsonic activity is not detectable in the 3E4/H8+ non-protective Ig population. In addition, results indicate that the 3E4/H8+ non-protective Ig population competes with protective opsonic 3A2/G6+ Ig antibodies when co-incubated with parasitized red blood cells. Thus, it follows that protection can be directly correlated to the quantitative and qualitative fluctuation of the two Ig populations. When challenged with 1 x 10(8) P. falciparum-infected Saimiri red blood cells parasitemia occurred in 5 out of 12 Saimiri who were lacking detectable 3A2/G6+ opsonic antibodies in their sera. By employing antibodies against the human Fc receptor for IgG (Fc gamma R) in an in vitro phagocytic assay, we have been able to show that the principal receptor is Fc gamma RIII. Finally, we also show that in contrast to the situation in man, this receptor is present on circulating monocytes. These findings could lead to a different strategy in designing malaria vaccine candidates and also allow the possibility of predicting the outcome of immunization trials in Saimiri monkeys.

Animals↗

Impairment of monocyte functions in advanced head and neck cancer.

Depression of cell-mediated immunity is well established in most malignancies and especially in head and neck cancers, and much information is available concerning the defect in helper T lymphocyte function. We now report on impairment of the monocyte-macrophage system. Compared with normal controls we found that patients displayed, on one hand, an increased number of peripheral blood monocytes and, on the other hand, a smaller percentage of HLA-DR+ monocytes. Such peripheral blood monocytes normally failed to secrete factors, including interleukin 1 (IL-1). In addition, we observed that the in vivo induced blastogenesis of peripheral blood lymphocytes from patients, which is spontaneously depressed, is partly restored by medium containing IL-1. We cannot exclude, however, that the observed monocyte dysfunction involves other cytokines. Whether such an immune deficiency is due to secondary malnutrition or to the malignancy (or both) remains unclear.

Adult↗

Interleukin-2 receptor is functionally linked with in vitro activation of B cells isolated from non-Hodgkin's lymphomas.

Proliferation and differentiation of B cells can be promoted by a number of inducing factors, including interleukin-2 (IL-2). In vitro-stimulated normal B cells usually express IL-2 receptors (TAC). Furthermore, it has been reported that some minor sub-populations of B cells in normal lymphoid tissue also express TAC antigen, as do some leukemic B cells. In the present study, the reactivity of 20 specimens of non-Hodgkin's lymphoma or B-cell origin was examined for a wide panel of monoclonal antibodies (MAb), including an anti-TAC MAb. The ability of the isolated and purified B cells to proliferate in the presence of B-cell mitogens and culture supernatants (containing various growth factors, including IL-2) was also investigated. These experiments provided some evidence that the TAC-negative cells remained unreactive, whereas the TAC-positive cells entered the cell cycle and proliferated. IL-2 responsiveness of neoplastic B cells is therefore discussed.

Antibodies, Monoclonal↗

Detection of CD1 positive cells in the peripheral blood of patients suffering from cancer-associated malnutrition.

The immunological phenotyping of peripheral blood mononuclear cells (PBMC) was assayed in a series of 22 patients suffering from severe cancer-associated malnutrition. A marked decrease of the T-lymphocyte subsets (CD3+, CD4+, CD8+) and of the CD20+ B lymphocytes occurred; there was however an increased percentage of monocytes but their absolute number was normal. Interestingly, 5% of the PBMC expressed "activated T-cell antigens". The specificity of two different monoclonal antibodies (MoAbs) towards CD1 epitopes (OKT6 and D47) was assessed by indirect immunofluorescence (IIF): about 5% of CD1+ thymocytes were detected with no antigen (Ag) cross reactivity with the small subset of activated T cells. It is hypothesized that some relationship may exist between such cells and malnutrition and/or cancer.

Adult↗

Distinct entities among low-grade non-Hodgkin's malignant lymphomas. Analysis of a series of 377 cases.

A series of 377 low-grade non-Hodgkin's lymphomas, observed in the same Institute, was analysed. Pathological types following the Kiel classification were crossed with the usual parameters of patients (sex, age) and disease (tumoural extension, main anatomical involvement, biological data, course of the disease). Small differences appeared for the survivals for the overall series. By contrast many significant differences were observed for sex, age, dissemination of the disease, special tissue involvement, monoclonal gammopathy, complete remission rate and further involvement in case of relapse. These parameters allow one to distinguish different clinicopathological entities after the morphological cellular features. Such correspondences appear meaningful and might be offered by any other classification which should not be based only on the prognosis.

Age Factors↗

[Acute rheumatic fever in New Caledonia. Clinical and epidemiological aspects].

Rheumatic fever is frequently encountered in tropical countries. Its distribution, incidence and consequences, notably on the heart, were studied in Nouvelle-Calédonie (South Pacific) on the basis of 76 patients with acute attack. The data were compared with those obtained in controls of the same age, sex and ethnic origin. Many patients developed carditis (often disabling), and relapses were frequent. The epidemiological data confirmed that rheumatic fever preferentially affects young subjects of both sexes and is more common among Melanesians and Polynesians, probably because of their lower socio-economic status.

Adolescent↗

T cell subsets in rheumatic fever in New Caledonia.

T cell subsets were evaluated in 76 New-Caledonian patients with recent onset rheumatic fever. A significant but modest decrease of OKT4+ cells and increase of OKT8+ cells was noted, leading to a decreased OKT4/OKT8 ratio. These changes were observed irrespective of the presence of carditis.

Antibodies, Monoclonal↗

A follow up of T-cell subsets and of anti-M. leprae antibody titer as measured by the FLA-ABS test in Melanesian leprosy patients under polychemotherapy.

Melanesian leprosy patients from New Caledonia were studied for the following parameters during the course of polychemotherapy: peripheral blood T-cell subsets, as identified in an immunofluorescence assay with monoclonal antibodies OKT3 ("pan-T"), OKT4 ("helper/inducer"), and OKT8 ("cytotoxic-suppressor"), and anti-Mycobacterium leprae antibodies in the serum, as measured by the fluorescent leprosy antibody absorption test. A group of Melanesian healthy subjects with no known exposure to M. leprae served as controls. Healthy contacts of leprosy patients were also studied for the presence of anti-M. leprae antibodies. Untreated, nonreactional lepromatous patients displayed moderate but significant T-cell abnormalities, consisting of a decrease in the percentage of OKT3+ and OKT4+ cells with a decrease in the OKT4:OKT8 ratio. These abnormalities disappeared within nine months of treatment. A transient decrease in the percentage of OKT8+ cells with an increase in the OKT4:OKT8 ratio was seen in patients suffering erythema nodosum leprosum (ENL). Tuberculoid patients, whether treated or not, did not show any T-cell marker disturbances. Positive serological tests for anti-M. leprae antibodies were found in 100% of lepromatous patients, 92% of tuberculoid patients, and 56% of healthy contacts. No significant decline in the antibody titer was observed with treatment during the survey period.

Adolescent↗