F. Modabber - Academia.edu (original) (raw)

Papers by F. Modabber

Infection and Immunity, 2001

Leishmania major is a protozoan parasite that causes chronic cutaneous lesions that often leave d... more Leishmania major is a protozoan parasite that causes chronic cutaneous lesions that often leave disfiguring scars. Infections in mice have demonstrated that leishmanial vaccines that include interleukin-12 (IL-12) as an adjuvant are able to induce protective immunity. In this study, we assessed the safety, immunopotency, and adjuvant potential of two doses of IL-12 when used with a killed L. major vaccine in vervet monkeys. The induction of cell-mediated immunity following vaccination was determined by measuring delayed-type hypersensitivity, in vitro lymphocyte proliferation, and gamma interferon (IFN-γ) production. Protection was assessed by challenging the animals with L. major parasites and monitoring the course of infection. At low doses of IL-12 (10 μg), a small increase in the parameters of cell-mediated immunity was observed, relative to those in animals that received antigen without IL-12. However, none of these animals were protected against a challenge infection. At highe...

Clinical and experimental immunology, 1986

BALB/c mice are highly susceptible to Leishmania major infection and develop a disseminated letha... more BALB/c mice are highly susceptible to Leishmania major infection and develop a disseminated lethal disease. Previous experiments indicate that during infection the spleen is heavily populated with large mononuclear cells containing amastigotes. Morphologically these cells resemble undifferentiated monocytes and granulocytes. In this study we examined myelopoiesis in BALB/c and C57BL/6 (resistant) mice during infection with L. major. The number of macrophage-granulocyte precursors in the spleen of infected BALB/c mice, determined by colony forming units in soft-agar cultures (cfu-c), increased steadily to a level of about 60 times that of normal sex- and age-matched controls. In C57BL/6 mice, spleen cfu-c peaked at about 1 month post-infection (four times that of normal controls) and declined thereafter to about two times normal levels. The number of cfu-c in the bone marrow did not change significantly in either strain during the infection. Colony stimulating activity (CSA) was foun...

Journal of immunology, 1976

The results reported in this paper demonstrate that the enumeration of cells binding beta-galacto... more The results reported in this paper demonstrate that the enumeration of cells binding beta-galactosidase (Z) as an antigen, revealed by subsequent substrate hydrolysis, is an excellent method for the detection and study of antigen-binding cells (ZBC). The binding found is specific and is restricted to a small number of lymphocytes that bind a large number of Z molecules via surface receptors. Such ZBC were found at mean frequencies of 150 per 10(6) in the thymus and 200 to 300 per 10(6) in the spleen. The binding cells of both organs were heterogenous with individual ZBC binding from 10(5) to 10(6) molecules of enzyme as determined by substrate hydrolysis, although this might well be an overestimate of the number of actual receptors. The profiles for the frequency of ZBC binding different numbers of molecules were nearly identical for thymus and spleen, in contrast to descriptions of the binding of many other antigens. Receptors responsible for Z binding appear to be superficially lo...

Clinical and experimental immunology, 1981

The visceral and lethal infection produced in BALB/c mice by Leishmania tropica (major) is accomp... more The visceral and lethal infection produced in BALB/c mice by Leishmania tropica (major) is accompanied by splenomegaly, anaemia and reversal of albumin-to-globulin ratio. The percentages of both B and T cells are decreased in the spleen. The spleen and lymph nodes become populated with large Ig-, Thy 1.2- 'null' cells. The similarity of some of these parameters with those produced in human kala-azar is discussed.

Journal of immunology, 1976

The results reported in this paper suggest that the specific Z-binding cells of the normal mouse ... more The results reported in this paper suggest that the specific Z-binding cells of the normal mouse include a large portion of T lymphocytes. Depletion of T cells with anti-theta serum and cortisone indicates that the majority of the ZBC of the thymus, which occur at frequencies of about 150/10(6), are indeed T cells. Similar treatment of spleen cells suggests that approximately half the binding cells in that organ are contributed by the T lymphocyte population. T-and B-enriched populations obtained from the spleen by using differential adherence to nylon wool contained equal numbers of ZBC and bound equivalent amounts of the antigen. Hence, there appears to be a high frequency of T lymphocytes that can be shown to bind beta-galactosidase specifically in both the thymus and spleen of normal mice.

The susceptibility of various strains of mice to infection by Leishmania tropica (major) was rece... more The susceptibility of various strains of mice to infection by Leishmania tropica (major) was recently studied in this laboratory. The infection in A/J, C3H, CBA, AKR/J, AKR/CU, and C57B1 mice (the semi resistant strains) remained cutaneous and the animals recovered within 4-6 months. However BALB/c mice developed generalized infection after two months of exposure resulting in death 3-4 months later. When compared to the semi resistant strains, BALB/c mice exhibited a poor delayed hypersensitivity (DH) to Leishmania antigen, but a relatively higher humoral response. In this study, the effect of levamisole on modulation of cell mediated immunity, d well as regulation of disease in A/J and BALB/c mice was investigat6d and compared: 1. Thirty days after infection, the titer of antibody in levamisole treated A/J or BALB/c mice was similar to the corresponding untreated control. However, when compared to the controls, the magnitude of DH was decreased in levamisole treated A/J mice but pa...

A vaccine against leishmaniasis is the only practical means to control this disease in many epide... more A vaccine against leishmaniasis is the only practical means to control this disease in many epidemiological situations. Two approaches have been adopted: pragmatic and systematic. The pragmatic approach involves trial of crude leishmanial components in animals and then in humans if they meet safety requirements. The systematic approach requires identification of the protective immunogen(s), appropriate carrier and adjuvant, and determination of the immune responses and modes of presentation of the immunogens to achieve the desired effect. Progress have been made with both approaches. Killed Leishmania promastigotes have been used in Brazil for high risk individuals with encouraging results. Impressive results have also been observed with killed Leishmania plus BCG for immunotherapy of cutaneous leishmaniasis in Venezuela. With the systematic approach, recent research has identified some protective immunogens, cloned protective murine T-cells, developed primate models resembling the ...

The ability of cell suspensions from spleen to bind antibody raised against β-galactosidase of Es... more The ability of cell suspensions from spleen to bind antibody raised against β-galactosidase of Escherichia coli was tested in vitro . To exclude macrophage binding most macrophages were removed by their adherence property from the spleen cell suspensions, and the lymphocyte-rich fraction was used to test for cytophilic antibody. Hundreds of 0.2-µl droplets containing 30 to 40 cells were made in oil chambers; the number of such cells was chosen so that macrophages would be statistically excluded from one-third of the total drops. The antigen-binding activity of cells treated with antiserum in those droplets containing no macrophages was calculated, and lymphocytes from spleen were shown to bind cytophilic antibody. In addition, thymocytes were also able to bind antibody and the binding as shown to be inhibited by exposing the cells to normal mouse serum. This indicated that the receptors for cytophilic binding on thymus cells could be preempted by molecules present in normal serum. T...

... in large measure to the organizational efficiency of IDRC's Conference Coordinators Lyse... more ... in large measure to the organizational efficiency of IDRC's Conference Coordinators Lyse Lavictoire and Julie Lalonde, and to Angie Anton of ... 119 Present Status of Leishmaniasis in Panama 128 JR Arias Distribution of Leishmaniasis in Peru 135 H. Guerra Andean Cutaneous ...

Molecular immunology, 1983

Monoclonal antibodies to MDP were prepared by hybridization of NSO myeloma cells with spleen cell... more Monoclonal antibodies to MDP were prepared by hybridization of NSO myeloma cells with spleen cells of BALB/c mice immunized with MDP conjugated to methyl-BSA. Hybridomas secreting anti-MDP antibodies were selected by the binding activity of their supernates to MDP-A--L using a radioimmunoassay. After cloning in soft agar, the specificities of monoclonal anti-MDP antibodies were assayed by an inhibition of ELISA with various derivatives of MDP. Fine structural analysis of specificity for one such clone (2-4) is reported. This antibody recognizes the N-acetyl-muramic acid (N-Ac-Mur) linked to the dipeptide but not N-Ac-Mur or/and dipeptide alone. The N-Ac group on muramic acid is an important antigenic determinant and the glycopeptide linkage seems to be crucial in presenting the sugar moiety. Conservative substitution of L-Ala (i.e. by L-Ser or L-Val) had no effect on the binding ability to the antibody whereas a radical change, i.e. replacement of L-Ala by L-Pro or N-methyl-L-Ala co...

Annals of Tropical Medicine & Parasitology, 1995

... advantages and disadvantages of each approach to vaccine development are discussed and the pr... more ... advantages and disadvantages of each approach to vaccine development are discussed and the progress being made is briefly reviewed. Formats. Abstract. Full Text. PDF. ... Search by Subject. ... UK PubMed Central is a service of the UKPMC Funders Group working in partnership ...

The Indian Journal of Medical Research, Mar 1, 2006

A vaccine against different forms of leishmaniasis should be feasible considering the wealth of i... more A vaccine against different forms of leishmaniasis should be feasible considering the wealth of information on genetics and biology of the parasite, clinical and experimental immunology of leishmaniasis, and the availability of vaccines that can protect experimental animals against challenge with different Leishmania species. However, there is no vaccine against any form of leishmaniasis for general human use. One major factor is the lack of a conceived market for human leishmaniasis vaccines. Hence pharmaceutical industries involved in vaccine development are not interested in investing millions of dollars and a decade that is required for developing a new vaccine. Besides, leishmaniasis is a local/regional problem and not a global one. According to the estimates of the World Health Organization, 90 per cent of visceral leishmaniasis occurs in five countries (Bangladesh, Brazil, India, Nepal and Sudan). Those in need are amongst the poorest people in these countries. It should therefore be the objectives of these countries to develop a vaccine. Fortunately, both Brazil and India have designated the control of visceral leishmaniasis as a top priority for their respective Ministries of Health. The purpose of this review is to present only the vaccines in use and those in development for use in dogs or humans. This is not an exhaustive review of vaccine discovery or the principles of clinical immunology underlying vaccine development.

The Journal of Immunology, Aug 1, 1970

Trans Roy Soc Trop Med Hyg, 2005

Infection and Immunity, 2001

Leishmania major is a protozoan parasite that causes chronic cutaneous lesions that often leave d... more Leishmania major is a protozoan parasite that causes chronic cutaneous lesions that often leave disfiguring scars. Infections in mice have demonstrated that leishmanial vaccines that include interleukin-12 (IL-12) as an adjuvant are able to induce protective immunity. In this study, we assessed the safety, immunopotency, and adjuvant potential of two doses of IL-12 when used with a killed L. major vaccine in vervet monkeys. The induction of cell-mediated immunity following vaccination was determined by measuring delayed-type hypersensitivity, in vitro lymphocyte proliferation, and gamma interferon (IFN-γ) production. Protection was assessed by challenging the animals with L. major parasites and monitoring the course of infection. At low doses of IL-12 (10 μg), a small increase in the parameters of cell-mediated immunity was observed, relative to those in animals that received antigen without IL-12. However, none of these animals were protected against a challenge infection. At highe...

Clinical and experimental immunology, 1986

BALB/c mice are highly susceptible to Leishmania major infection and develop a disseminated letha... more BALB/c mice are highly susceptible to Leishmania major infection and develop a disseminated lethal disease. Previous experiments indicate that during infection the spleen is heavily populated with large mononuclear cells containing amastigotes. Morphologically these cells resemble undifferentiated monocytes and granulocytes. In this study we examined myelopoiesis in BALB/c and C57BL/6 (resistant) mice during infection with L. major. The number of macrophage-granulocyte precursors in the spleen of infected BALB/c mice, determined by colony forming units in soft-agar cultures (cfu-c), increased steadily to a level of about 60 times that of normal sex- and age-matched controls. In C57BL/6 mice, spleen cfu-c peaked at about 1 month post-infection (four times that of normal controls) and declined thereafter to about two times normal levels. The number of cfu-c in the bone marrow did not change significantly in either strain during the infection. Colony stimulating activity (CSA) was foun...

Journal of immunology, 1976

The results reported in this paper demonstrate that the enumeration of cells binding beta-galacto... more The results reported in this paper demonstrate that the enumeration of cells binding beta-galactosidase (Z) as an antigen, revealed by subsequent substrate hydrolysis, is an excellent method for the detection and study of antigen-binding cells (ZBC). The binding found is specific and is restricted to a small number of lymphocytes that bind a large number of Z molecules via surface receptors. Such ZBC were found at mean frequencies of 150 per 10(6) in the thymus and 200 to 300 per 10(6) in the spleen. The binding cells of both organs were heterogenous with individual ZBC binding from 10(5) to 10(6) molecules of enzyme as determined by substrate hydrolysis, although this might well be an overestimate of the number of actual receptors. The profiles for the frequency of ZBC binding different numbers of molecules were nearly identical for thymus and spleen, in contrast to descriptions of the binding of many other antigens. Receptors responsible for Z binding appear to be superficially lo...

Clinical and experimental immunology, 1981

The visceral and lethal infection produced in BALB/c mice by Leishmania tropica (major) is accomp... more The visceral and lethal infection produced in BALB/c mice by Leishmania tropica (major) is accompanied by splenomegaly, anaemia and reversal of albumin-to-globulin ratio. The percentages of both B and T cells are decreased in the spleen. The spleen and lymph nodes become populated with large Ig-, Thy 1.2- 'null' cells. The similarity of some of these parameters with those produced in human kala-azar is discussed.

Journal of immunology, 1976

The results reported in this paper suggest that the specific Z-binding cells of the normal mouse ... more The results reported in this paper suggest that the specific Z-binding cells of the normal mouse include a large portion of T lymphocytes. Depletion of T cells with anti-theta serum and cortisone indicates that the majority of the ZBC of the thymus, which occur at frequencies of about 150/10(6), are indeed T cells. Similar treatment of spleen cells suggests that approximately half the binding cells in that organ are contributed by the T lymphocyte population. T-and B-enriched populations obtained from the spleen by using differential adherence to nylon wool contained equal numbers of ZBC and bound equivalent amounts of the antigen. Hence, there appears to be a high frequency of T lymphocytes that can be shown to bind beta-galactosidase specifically in both the thymus and spleen of normal mice.

The susceptibility of various strains of mice to infection by Leishmania tropica (major) was rece... more The susceptibility of various strains of mice to infection by Leishmania tropica (major) was recently studied in this laboratory. The infection in A/J, C3H, CBA, AKR/J, AKR/CU, and C57B1 mice (the semi resistant strains) remained cutaneous and the animals recovered within 4-6 months. However BALB/c mice developed generalized infection after two months of exposure resulting in death 3-4 months later. When compared to the semi resistant strains, BALB/c mice exhibited a poor delayed hypersensitivity (DH) to Leishmania antigen, but a relatively higher humoral response. In this study, the effect of levamisole on modulation of cell mediated immunity, d well as regulation of disease in A/J and BALB/c mice was investigat6d and compared: 1. Thirty days after infection, the titer of antibody in levamisole treated A/J or BALB/c mice was similar to the corresponding untreated control. However, when compared to the controls, the magnitude of DH was decreased in levamisole treated A/J mice but pa...

A vaccine against leishmaniasis is the only practical means to control this disease in many epide... more A vaccine against leishmaniasis is the only practical means to control this disease in many epidemiological situations. Two approaches have been adopted: pragmatic and systematic. The pragmatic approach involves trial of crude leishmanial components in animals and then in humans if they meet safety requirements. The systematic approach requires identification of the protective immunogen(s), appropriate carrier and adjuvant, and determination of the immune responses and modes of presentation of the immunogens to achieve the desired effect. Progress have been made with both approaches. Killed Leishmania promastigotes have been used in Brazil for high risk individuals with encouraging results. Impressive results have also been observed with killed Leishmania plus BCG for immunotherapy of cutaneous leishmaniasis in Venezuela. With the systematic approach, recent research has identified some protective immunogens, cloned protective murine T-cells, developed primate models resembling the ...

The ability of cell suspensions from spleen to bind antibody raised against β-galactosidase of Es... more The ability of cell suspensions from spleen to bind antibody raised against β-galactosidase of Escherichia coli was tested in vitro . To exclude macrophage binding most macrophages were removed by their adherence property from the spleen cell suspensions, and the lymphocyte-rich fraction was used to test for cytophilic antibody. Hundreds of 0.2-µl droplets containing 30 to 40 cells were made in oil chambers; the number of such cells was chosen so that macrophages would be statistically excluded from one-third of the total drops. The antigen-binding activity of cells treated with antiserum in those droplets containing no macrophages was calculated, and lymphocytes from spleen were shown to bind cytophilic antibody. In addition, thymocytes were also able to bind antibody and the binding as shown to be inhibited by exposing the cells to normal mouse serum. This indicated that the receptors for cytophilic binding on thymus cells could be preempted by molecules present in normal serum. T...

... in large measure to the organizational efficiency of IDRC's Conference Coordinators Lyse... more ... in large measure to the organizational efficiency of IDRC's Conference Coordinators Lyse Lavictoire and Julie Lalonde, and to Angie Anton of ... 119 Present Status of Leishmaniasis in Panama 128 JR Arias Distribution of Leishmaniasis in Peru 135 H. Guerra Andean Cutaneous ...

Molecular immunology, 1983

Monoclonal antibodies to MDP were prepared by hybridization of NSO myeloma cells with spleen cell... more Monoclonal antibodies to MDP were prepared by hybridization of NSO myeloma cells with spleen cells of BALB/c mice immunized with MDP conjugated to methyl-BSA. Hybridomas secreting anti-MDP antibodies were selected by the binding activity of their supernates to MDP-A--L using a radioimmunoassay. After cloning in soft agar, the specificities of monoclonal anti-MDP antibodies were assayed by an inhibition of ELISA with various derivatives of MDP. Fine structural analysis of specificity for one such clone (2-4) is reported. This antibody recognizes the N-acetyl-muramic acid (N-Ac-Mur) linked to the dipeptide but not N-Ac-Mur or/and dipeptide alone. The N-Ac group on muramic acid is an important antigenic determinant and the glycopeptide linkage seems to be crucial in presenting the sugar moiety. Conservative substitution of L-Ala (i.e. by L-Ser or L-Val) had no effect on the binding ability to the antibody whereas a radical change, i.e. replacement of L-Ala by L-Pro or N-methyl-L-Ala co...

Annals of Tropical Medicine & Parasitology, 1995

... advantages and disadvantages of each approach to vaccine development are discussed and the pr... more ... advantages and disadvantages of each approach to vaccine development are discussed and the progress being made is briefly reviewed. Formats. Abstract. Full Text. PDF. ... Search by Subject. ... UK PubMed Central is a service of the UKPMC Funders Group working in partnership ...

The Indian Journal of Medical Research, Mar 1, 2006

A vaccine against different forms of leishmaniasis should be feasible considering the wealth of i... more A vaccine against different forms of leishmaniasis should be feasible considering the wealth of information on genetics and biology of the parasite, clinical and experimental immunology of leishmaniasis, and the availability of vaccines that can protect experimental animals against challenge with different Leishmania species. However, there is no vaccine against any form of leishmaniasis for general human use. One major factor is the lack of a conceived market for human leishmaniasis vaccines. Hence pharmaceutical industries involved in vaccine development are not interested in investing millions of dollars and a decade that is required for developing a new vaccine. Besides, leishmaniasis is a local/regional problem and not a global one. According to the estimates of the World Health Organization, 90 per cent of visceral leishmaniasis occurs in five countries (Bangladesh, Brazil, India, Nepal and Sudan). Those in need are amongst the poorest people in these countries. It should therefore be the objectives of these countries to develop a vaccine. Fortunately, both Brazil and India have designated the control of visceral leishmaniasis as a top priority for their respective Ministries of Health. The purpose of this review is to present only the vaccines in use and those in development for use in dogs or humans. This is not an exhaustive review of vaccine discovery or the principles of clinical immunology underlying vaccine development.

The Journal of Immunology, Aug 1, 1970

Trans Roy Soc Trop Med Hyg, 2005