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For the development of vaccine strategies to generate efficient protection against chronic infections such as parasitic diseases, and more precisely schistosomiasis, controlling pathology could be more relevant than controlling the infection itself. Such strategies, motivated by the need for a cost-effective complement to existing control measures, should focus on parasite molecules involved in fecundity, because in metazoan parasite infections pathology is usually linked to the output of viable eggs. In numerous animal models, vaccination with glutathione S-transferases of 28kDa has been shown to generate an immune response strongly limiting the worm fecundity, in addition to the reduction of the parasite burden. Recent data on acquired immunity directed to 28GST in infected human populations, and new development to draw adapted vaccine formulations, are presented.

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The dual function of eosinophils has been evidenced in protective immunity against parasites as well as in pathological manifestations during allergic disorders. We have demonstrated that a new class of IgE receptors, Fc epsilon RII/CD23, was involved in the functional duality of eosinophils and other proinflammatory cells. More recently, we have shown that Fc epsilon RI, the high affinity IgE receptor thought to be only expressed by basophils and most cells, was involved in eosinophil-mediated cytotoxicity against schistosomes as well as in mediator release. These results favour the view that both IgE and its receptors have been primarily associated to a protective immune response, rather than to pathology. Not only IgE receptors but also members belonging to the family of adhesion molecules can participate as co-receptors in eosinophil effector function. The inhibitory role of monoclonal antibodies to Lewis(X) (Le(X) CD15) or to selectins in eosinophil-mediated cytotoxicity towards schistosomes and the detection of Le(X) and selectin-like molecules on schistosomula surface indicate a double interaction mediated by selectins and their carbohydrate ligands between eosinophils and schistosomula. These results suggest new functions for these adhesion molecules, previously known to be involved mainly in cell infiltration.

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Schistosomiasis is a chronic and debilitating parasitic disease that affects over 200 million people throughout the world and causes about 500,000 deaths annually. Two specific characteristics of schistosome infection are of primordial importance to the development of a vaccine: schistosomes do not multiply within the tissues of their definitive hosts (unlike protozoan parasites) and a partial non-sterilizing immunity can have a marked effect on the incidence of pathology and on disease transmission. Since viable eggs are the cause of disease pathology, a reduction in worm fecundity whether or not accompanied by a reduction in parasite burden is a sufficient goal for vaccine induced immunity. We originally showed that IgE antibodies played in experimental models a pivotal role for the development of protective immunity. These laboratory findings have been now confirmed in human populations. Following the molecular cloning and expression of a protein 28 kDa protein of Schistosoma mansoni and its identification as a glutathion S-transferase, immunization experiments have been undertaken in several animal species (rats, mice, baboons). Together with a significant reduction in parasite burden, vaccination with Sm28 GST was recently shown to reduce significantly parasite fecundity and egg viability leading to a decrease in liver pathology. Whereas IgE antibodies were shown to be correlated with protection against infection, IgA antibodies have been identified as one of the factors affecting egg laying and viability. In human populations, a close association was found between IgA antibody production to Sm28 GST and the decrease of egg output.(ABSTRACT TRUNCATED AT 250 WORDS)

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Schistosomiasis, the second major parasitic disease in the world after malaria affects at least 200 million people, 500 million being exposed to the risk of infection. It is widely agreed that a vaccine strategy which could lead to the induction of effector mechanisms reducing the level of reinfection and ideally parasite fecundity would deeply affect the incidence of pathological manifestations as well as the parasite transmission potentialities. Extensive studies performed in the rat model have allowed the identification of novel effector mechanisms involving IgE antibodies and various inflammatory cell populations (eosinophils, macrophages and platelets) whereas regulation of immune response by blocking antibodies has been evidenced. Recent epidemiological studies have now entirely confirmed in human populations the role of IgE antibodies in the acquisition of resistance and the association of IgG4 blocking antibodies with increased susceptibility. On the basis of these concepts, several schistosome target proteins have been identified and their encoding genes cloned. One of them, a schistosome glutathione S-transferase (Sm 28 GST) appears as a promising vaccine candidate. Immunization experiments have shown that two complementary goals can be achieved: (a) a partial but significant reduction of the worm population (up to 60% in rats); (b) a significant reduction of parasite fecundity (up to 70% in mice and 85% in cattle) and egg viability (up to 80%). At least two distinct immunological mechanisms account for these two effects. IgE antibodies appear as a major humoral component of acquired resistance whereas IgA antibodies appear as a major humoral factor affecting parasite fecundity.(ABSTRACT TRUNCATED AT 250 WORDS)

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The dual function of eosinophils is clearly illustrated in schistosomiasis. Well equipped in membrane receptors for immunoglobulins and complement, and due to the presence of granule basic proteins, eosinophils can become cytotoxic for parasite larvae and thus participate to protective immunity. However, mediators can also exert their cytolytic effect on normal cells or tissues, inducing therefore pathology. through ADCC mechanisms against schistosome larvae in vitro involving different antibody isotypes (IgG, IgE and IgA) and also in experiments performed in vivo, eosinophils have been clearly involved in protective immunity. Although no direct evidence of the protective role of eosinophils were brought in humans, the striking association of eosinophil-dependent cytotoxic antibody isotypes with resistance to reinfection (for instance IgE and IgA antibodies), whereas in vitro blocking antibody isotypes (IgG4, IgM) were detected in susceptible subjects, strongly, suggested the participation of eosinophils in antibody-dependent protective immune response. However eosinophils could also participate to granuloma formation around S. mansoni eggs and consequently to the pathological reactions induced by schistosomiasis.

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In this review the authors analyze the effector and regulatory mechanisms in the immune response to schistosomiasis. To study these mechanisms two animal models were used, mouse and rat. The mouse totally permissive host like human, show prominent-T cell control in the acquisition of resistance. But other mechanisms like antibody mediated cytotoxicity (ADCC) involving eosinophils and IgG antibodies described in humans, are observed in rats. Also in this animal, it is observed specific IgE antibody high production and blood and tissue eosinophilia. Using the rat model and schistosomula as target, some ADCC features have emerged: the cellular population involved are bone marrow derived inflammatory cell (mononuclear phagocytes, eosinophils and platelets), interacting with IgE through IgE Fc receptors. Immunization has been attempted using the recombinant protein Sm28/GST. Protection has been observed in rodents with significant decrease of parasite fecundity and egg viability affecting the number, size and volume of liver egg granulomas. The association of praziquantel and immunization with Sm28/GST increases the resistance to infection and decreases egg viability. The authors suggest the possibility of the establishment of a future vaccine against Schistosoma mansoni.

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In this review the authors analyze the effector and regulatory mechanisms in the immune response to schistosomiasis. To study these mechanisms two animal models were used, mouse and rat. The mouse totaly permissive host like human, show prominent-T cell control in the acquisition of resistance. But other mechanisms like antibody mediated cytotoxity (ADCC) involving eosinophils and IgG antibodies described in humans, are observed in rats. Also in this animal, it is observed specific IgE antibody high production and blood and tisssue eosinophilia. Using the rat model and schistosomula as target, some ADCC features have emerged: the cellular population involved are bone marrow derived inflammatory cell (mononuclear phagocytes, eosinophils and platelets), interacting with IgE through IgE Fc receptors. Immunization has been attempted using the recombinant protein Sm28/GST. Protection has been observed in rodents with significant decrease of parasite fecundity and egg viability affecting the number, size and volume of liver egg granulomas. The association of praziquantel and immunization with with Sm28/GST increases the resistance to infection and decreases egg viability. The authors suggest the possibility of the stablishment of a future vaccine against Schistosoma mansoni

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Schistosomiasis, the second major parasitic disease in the world after malaria affects at least 200 million people, 500 million being exposed to the risk of infection. It is widely agreed that a vaccine strategy wich could lead to the induction of effector mechanisms reducing the level of reinfection and ideally parasite fecundity would deeply affect the incidence of pathological manifestations as well as the parasite transmission potentialities. Extensive studies performed in the rat model have allowed the identification of novel effector mechanisms involving IgE antibodies and various inflammatory cell populations (eosinophils, macrophages and platelets) whereas regulation of immune response by blocking antibodies has been evidencial. Recent epidemiological studies have now entirely confirmed in human populations the the role of IgE antibodies in the acquisition of resistance and the association of IgG4 blocking antibodies with increased susceptibility. On the basis of these concepts, several schistosome glutathion S-transferase (Sm 28 GST) appears as a pronising vaccine candidate. Immunization experiments have shown that two complementary goals can be achieved: (a) a partial but significant reduction of the worm population (up to 60//in rats); (b) a significant reduction of parasite fecundity (up in the mice and 85//in cattle) and egg viability (up to 80//). At least two distinct immunological mechanisms account for these two effects. IgE antibodies appear as a major humoral component of acquired resistance whereas IgA antibodies appear as a major humoral factor affecting parasite fecundity. These studies seem to represent a parasite diseases through the identification of potentially protective antigens and of the components of the immune response which vaccination should aim at inducing

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En la isla caribeña de Guadalupe, donde hay una alta prevalencia de infección por el virus linfotrópico T humano del tipo 1 (HTLV-1), los métodos de diagnóstico dan lugar a muchos resultados positivos falsos que hay que verificar mediante pruebas adicionales largas y costosas. En el presente artículo se describe una manera simple de solucionar este problema. Consiste, primero, en extraer del suero de un paciente toda la IgG y sus inmunocomplejos circulantes (ICC) mediante un tratamiento con proteína G, para después detectar la presencia de IgA antivírica en el suero tratado usando las pruebas comerciales de ELISA y Western Blot con ligeras modificaciones

Disponible en inglés en Bull Pan Am. Health Organ 25(3):201-06, 1991

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In Guadeloupe, a Caribbean island with a high prevalence of HTLV-I infected subjects, the percentage of false positive results for HIV IgG is high, requiring additional time and expense for confirmatory tests. This article describes a simple way of overcoming this problem. First, all IgG and IgG immune complexes are removed by protein G treatment, and then IgA enzyme-linked immunosorbent assay (ELISA) and the Western blot test are performed with minor modification of commercially available kits.

PIP: Researchers wanted to determine whether they could do a more specific ELISA HIV test directed at IgA rather than IgG antibodies. So they 1st used streptococcal protein G to remove IgG from serum samples of 10 follow up patients from Guadeloupe who previously tested positive via ELISA for HIV-1/2 IgG and HTLV-I IgG. They did this to test sera for IgA. The protein G treatment resulted in a 99.9% reduction in the IgG concentration (12.21.7 mg/ml to .007-.017 mg/ml). After IgG depletion, the researchers noted no ELISA positive samples for HIV-1/2 or HTLV-I IgG. In fact, all the values were well below the cutoff levels. This result indicated that streptococcal protein G treatment followed by IgA ELISA is more specific than testing for IgG. The sera of 8 patients tested negative for HIV-1/2 IgA, but all tested positive for HTLV-1 IgA. This result showed that IgA may be more useful than IgG for also confirming retroviral infections. The sera of 2 patients were 44% and 27% above the cutoff level indicating that these patients had HIV-1/2 IgA antibodies. The researchers observed that protein G treatment suppressed all HIV-1/2 and HTLV-I IgG Western blot reactivity which confirmed the effectiveness of protein G treatment. Further the HIV IgG bands in the 8 false positive sera did not materialize at all suggesting that the IgG reactivity observed was most likely nonspecific. These results indicated that nonspecific HIV-1/2 IgG caused the false positive HIV-1/2 IgG ELISA results. In conclusion, in Caribbean countries where HTLV-1 infection can be as high as 13%, the more specific HIV IgA ELISA test should be used since its use saves time and money. Further it can do generalized testing for HTLV antibodies.

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In Guadeloupe, a Caribbean island with a high prevalence of HTLV-I infected subjects, the percentage of false positive results for HIV IgG is high, requiring additional time and expense for confirmatory tests. This article describes a simple way of overcoming this problem. First, all IgG and IgG immune complexes are removed by protein G treatment, and then IgA enzyme-linked immudosorbent assay (ELISA) and the Western blot test are performed with minor modification of commercially available kits

Available in spanish in Bol. Oficina Sanit. Panam 112(1):12-18, 1992

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An antigen factor (EF), thermostable and soluble in trichloroacetic acid was detected in the supernatant fluid of epimastigote cultures of Trypanosoma cruzi and in the sera of patients with acute Chagas disease. An hyperimmune antiserum to this antigenic factor was obtained in rabbits. The EF was revealed on the fibroblast surface membranes of rats infected with trypomastigotes, using the indirect immunofluorescence technique. The presence of EF in the sera of patients with acute Chagas disease as well as in the supernatant of epimastigotes culture at logarithmic phase, leads to its association with a process of parasite proliferation. Being EF a component of the parasite, its origin both in vitro and in vivo could be the result of an excretion-secretion of parasite or simply a result of the parasite's death. It can be postulated that the same as in other protozoic infection, EF could be used by T. cruzi in the process of cell penetration.

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Se detectó un factor antigénico, temoestable y soluble en ácido tricloroacético (TCA) en el sobrenadante de cultivo de epimatigotes de Trypanosoma cruzi en fase logarítmica y en los sueros de pacientes con enfermedad de Chagas aguda. Este antígeno fue revelado en la mambrana de superficie de fibroblastos de ratas cuando fueron infectados con trypomastigotes, utilizando la técnica de inmunofluorescencia indirecta. El sobrenadante de cultivo de epimastigotes en medio GLSH libre de células a 28-C fue acidificado a pH5, calentado a ebullición 30 min y luego precipitado con TCA, centrifugado y el sobrenadante tratado con éter de petróleo. La solución extraída fue dializada, concentrada, liofilizada y purificada por cromatografía de afinidad. El eluido fue liofilizado y este material fue denominado factor antígeno excretado (EF). Un antisuero hiperinmune contra estos factores antígenos fue obtenido en conejos. El 76,6% de los sueros correspondientes a pacientes con Chagas agudo demostraron poseer el EF por técnica de inmunodifusión doble (Tabla 1). Monocapas de fibroblastos de ratas infectados previamente con 3 ml de trypomastigotes en una concentración de 5 x 10**6 células/ml sometidas a una inmunofluorescencia indirecta con el antisuero hiperinmune demostraron la presencia del EF en las membranas celulares de fibroblastos infectados y no infectados..

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An antigen factor (EF), thermostable and soluble in trichloroacetic acid was detected in the supernatant fluid of epimastigote cultures of Trypanosoma cruzi and in the sera of patients with acute Chagas disease. An hyperimmune antiserum to this antigenic factor was obtained in rabbits. The EF was revealed on the fibroblast surface membranes of rats infected with trypomastigotes, using the indirect immunofluorescence technique. The presence of EF in the sera of patients with acute Chagas disease as well as in the supernatant of epimastigotes culture at logarithmic phase, leads to its association with a process of parasite proliferation. Being EF a component of the parasite, its origin both in vitro and in vivo could be the result of an excretion-secretion of parasite or simply a result of the parasites death. It can be postulated that the same as in other protozoic infection, EF could be used by T. cruzi in the process of cell penetration.

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Se detectó un factor antigénico, temoestable y soluble en ácido tricloroacético (TCA) en el sobrenadante de cultivo de epimatigotes de Trypanosoma cruzi en fase logarítmica y en los sueros de pacientes con enfermedad de Chagas aguda. Este antígeno fue revelado en la mambrana de superficie de fibroblastos de ratas cuando fueron infectados con trypomastigotes, utilizando la técnica de inmunofluorescencia indirecta. El sobrenadante de cultivo de epimastigotes en medio GLSH libre de células a 28-C fue acidificado a pH5, calentado a ebullición 30 min y luego precipitado con TCA, centrifugado y el sobrenadante tratado con éter de petróleo. La solución extraída fue dializada, concentrada, liofilizada y purificada por cromatografía de afinidad. El eluido fue liofilizado y este material fue denominado factor antígeno excretado (EF). Un antisuero hiperinmune contra estos factores antígenos fue obtenido en conejos. El 76,6% de los sueros correspondientes a pacientes con Chagas agudo demostraron poseer el EF por técnica de inmunodifusión doble (Tabla 1). Monocapas de fibroblastos de ratas infectados previamente con 3 ml de trypomastigotes en una concentración de 5 x 10**6 células/ml sometidas a una inmunofluorescencia indirecta con el antisuero hiperinmune demostraron la presencia del EF en las membranas celulares de fibroblastos infectados y no infectados..

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The study of the surface antigens of Leishmania braziliensis braziliensis revealed a great homogeneity among ten strains isolated from Bolivia and two reference strains from Brazil and Belize. A 72 kDa major protein, present in all L. b. braziliensis strains, was recognized by both cutaneous and mucocutaneous human sera, but was not recognized by Kala-azar and chagasic sera. No cross-reactive antigens were found among strains of Leishmania braziliensis guyanensis, Leishmania braziliensis panamensis, Leishmania mexicana amazonensis and Leishmania donovani chagasi testing these strains with hamster and human anti-L. b. braziliensis sera. Moreover, these strains possessed major antigens with molecular weights different from those of L. b. braziliensis strains. A microheterogeneity of L. b. braziliensis surface antigens was detected for the high molecular weight antigens and seemed to be related to the isoenzymic microheterogeneity.

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Foi usado um teste imunoenzimático competitivo para investigar a presença de anticorpos anticomponente 5 nos soros de sariguês, cäes, coelhos e ratos infectados com o Trypanosoma cruzi. Neste teste, foi utilizado um anticorpo monoclonal contra o antígeno 5 que é específico do T. cruzi. Também foram testados os soros de 51 pacientes venezuelanos com doença de Chagas. Apesar desses anticorpos näo serem detectados nos soros de cäes, ratos e sariguês infectados com o T. cruzi, alguns soros de coelhos infectados apresentaram resultados positivos porém em níveis próximos aos do limite de positividade do teste. Esses achados surgerem que a resposta imune em animais naturalmente ou experimentalmente infectados com o T. cruzi é diferente daquela que é observada na doença de Chagas humana

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