RESUMEN
PROBLEM: Pregnancy appears to favor maternal antibody production. In contrast, by damaging follicular helper T cells (TFH ), HIV-1 infection compromises protective humoural immune response. Therefore, we aimed to investigate the frequency of different TFH -like cells in HIV-infected pregnant women (PW) before and after antiretroviral (ARV) therapy. METHOD OF STUDY: Peripheral blood mononuclear cells, CD4+ T and B cells, were obtained from asymptomatic HIV-1-infected non-PW and PW just before and after ARV therapy. In some experiments, healthy HIV-1-negative PW were also tested. The frequency of different TFH -like cell subsets was determined by flow cytometry. The plasma titers of IgG anti-tetanus toxoid (TT), anti-HBsAg, and anti-gp41 were determined by ELISA. The in vitro production of total IgG, IL-21, and hormones (estrogen and progesterone) was quantified also by ELISA. RESULTS: Our results demonstrate that antiretroviral (ARV) therapy was more efficient in elevating the percentage of circulating IL-21-secreting TFH cells in HIV-1-infected pregnant women (PW) than in non-pregnant patients (nPW). Moreover, in co-culture systems, CD4+ T cells from ART-treated PW were more efficient in assisting B cells to produce IgG production. The in vivo anti-HBsAg IgG titers after ARV therapy were also significantly higher in PW, and their levels were directly associated with both IL-21+ TFH frequency and plasma concentration of estrogen. CONCLUSION: In summary, our results suggest that pregnancy favors the recovery of TFH -like cells after ARV therapy in HIV-1-infected women, which could help these mothers to protect their newborns from infectious diseases by transferring IgG across the placenta.
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Fármacos Anti-VIH/farmacología , Infecciones por VIH/inmunología , VIH-1 , Interleucinas/metabolismo , Complicaciones Infecciosas del Embarazo/inmunología , Células T Auxiliares Foliculares/metabolismo , Adulto , Fármacos Anti-VIH/uso terapéutico , Anticuerpos Antibacterianos/sangre , Formación de Anticuerpos/efectos de los fármacos , Linfocitos B/efectos de los fármacos , Recuento de Linfocito CD4 , Células Cultivadas , Técnicas de Cocultivo , Estrógenos/sangre , Femenino , Anticuerpos Anti-VIH/sangre , Proteína gp41 de Envoltorio del VIH/inmunología , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , VIH-1/inmunología , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Humanos , Inmunoglobulina G/sangre , Embarazo , Complicaciones Infecciosas del Embarazo/sangre , Progesterona/sangre , Toxoide Tetánico/inmunología , Adulto JovenRESUMEN
The successful production of new, safe, and effective vaccines that generate immunological memory is directly related to adjuvant feature, which is responsible for increasing and/or modulating the immune response. Several compounds display adjuvant activity, including carbohydrates. These compounds play important roles in the immune response, as well as having biocompatible properties in vaccine formulations. One such carbohydrate is xanthan gum, a polysaccharide that is produced by the plant-pathogenic bacterium Xanthomonas spp., which has adjuvant attributes. This study evaluated the immune response induced by xanthan gum associated with ovalbumin in BALB/c mice, which were subcutaneously immunized, in terms of antibody production (IgG1, IgG2a, IgG2b, and IgG3), and assessed the levels of IFN-γ in the splenocyte culture using indirect ELISA. Furthermore, we investigated in vitro cytotoxicity of xanthan in the embryo fibroblasts cell line of the NIH/3T3 mouse by MTT assay and propidium iodide uptake assay. The mice immunized with ovalbumin plus xanthan gum exhibited higher antibody IgG1 responses than control groups. Furthermore, the xanthan polysaccharide was capable of increasing the immunogenicity of antigens by producing IFN-γ and did not exhibit cytotoxicity effects in NIH/3T3 mouse fibroblast cells, considered a promising candidate for vaccine adjuvant.
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Adyuvantes Inmunológicos/farmacología , Formación de Anticuerpos/efectos de los fármacos , Inmunoglobulina G/inmunología , Interferón gamma/inmunología , Polisacáridos Bacterianos/farmacología , Animales , Línea Celular , Evaluación Preclínica de Medicamentos , Femenino , Ratones , Ratones Endogámicos BALB C , Células 3T3 NIH , Polisacáridos Bacterianos/inmunologíaRESUMEN
Subcutaneous administration of a low dose of adrenaline is used to prevent the early adverse reactions (EARs) induced by snake antivenoms. We used a rabbit model to study the effect of premedication with adrenaline on the potential of antivenoms to exert therapeutic effects and to induce late adverse reactions. We found that premedication with adrenaline did not change the heart rate or blood pressure of normal rabbits, but reduced the rise in temperature in rabbits previously sensitized with antivenom. Pharmacokinetic studies suggest that premedication with adrenaline does not affect the ability of the antivenom to exert the initial control of envenomation nor the susceptibility of rabbits to develop recurrence of antigenemia and envenomation. Our results also indicate that it is unlikely that premedication with adrenaline decreases the incidence of late reactions induced by the antivenom administration, although it reduces the extent of early reactions.
Asunto(s)
Formación de Anticuerpos/efectos de los fármacos , Formación de Anticuerpos/inmunología , Antivenenos/inmunología , Epinefrina/administración & dosificación , Caballos/inmunología , Inmunoglobulina G/inmunología , Ponzoñas/inmunología , Animales , Inyecciones Subcutáneas/métodos , Modelos Animales , Premedicación/métodos , ConejosRESUMEN
An experimental model of Guillain-Barré Syndrome has been established in recent years. Rabbits develop disease upon immunization with a single dose of an emulsion containing bovine brain gangliosides, KLH and complete Freund's adjuvant. Within a period of four to ten weeks after immunization, they began to produce anti-ganglioside IgG-antibodies first, and to show clinical signs of neuropathy afterwards. In addition to gangliosides, KLH is a requirement for antibody production and disease triggering. Although KLH is commonly used as an immunological carrier protein, an anti-KLH-specific immune response was necessary for induction of both events. KLH is a glycoprotein carrying most of the immunogenicity in its glycan moiety. Between 20% to 80% of anti-ganglioside IgG-antibodies present in sick rabbit sera cross-reacted with KLH, indicating that both immune responses are related. The terminal Gal-ß(1,3)-GalNAc glycan (present in gangliosides and KLH) is proposed as "key" antigenic determinant involved in inducing the anti-ganglioside immune response. These results are discussed in the context of the "binding site drift" hypothesis.
Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Formación de Anticuerpos/efectos de los fármacos , Síndrome de Guillain-Barré , Hemocianinas/efectos adversos , Inmunización/efectos adversos , Modelos Inmunológicos , Adyuvantes Inmunológicos/farmacología , Animales , Modelos Animales de Enfermedad , Síndrome de Guillain-Barré/inducido químicamente , Síndrome de Guillain-Barré/inmunología , Síndrome de Guillain-Barré/patología , Hemocianinas/farmacología , Humanos , ConejosRESUMEN
This study presents the synthesis of the novel protected O-glycosylated amino acid derivatives 1 and 2, containing ßGalNAc-SerOBn and ßGalNAc-ThrOBn units, respectively, as mimetics of the natural Tn antigen (αGalNAc-Ser/Thr), along with the solid-phase assembly of the glycopeptides NHAcSer-Ala-Pro-Asp-Thr[αGalNAc]-Arg-Pro-Ala-Pro-Gly-BSA (3-BSA) and NHAcSer-Ala-Pro-Asp-Thr[ßGalNAc]-Arg-Pro-Ala-Pro-Gly-BSA (4-BSA), bearing αGalNAc-Thr or ßGalNAc-Thr units, respectively, as mimetics of MUC1 tumor mucin glycoproteins. According to ELISA tests, immunizations of mice with ßGalNAc-glycopeptide 4-BSA induced higher sera titers (1:320 000) than immunizations with αGalNAc-glycopeptide 3-BSA (1:40 000). Likewise, flow cytometry assays showed higher capacity of the obtained anti-glycopeptide 4-BSA antibodies to recognize MCF-7 tumor cells. Cross-recognition between immunopurified anti-ßGalNAc antibodies and αGalNAc-glycopeptide and vice versa was also verified. Lastly, molecular dynamics simulations and surface plasmon resonance (SPR) showed that ßGalNAc-glycopeptide 4 can interact with a model antitumor monoclonal antibody (SM3). Taken together, these data highlight the improved immunogenicity of the unnatural glycopeptide 4-BSA, bearing ßGalNAc-Thr as Tn antigen isomer.
Asunto(s)
Anticuerpos Monoclonales/metabolismo , Formación de Anticuerpos/efectos de los fármacos , Antígenos de Carbohidratos Asociados a Tumores/química , Mucina-1/metabolismo , Mucina-1/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Bioensayo/normas , Secuencia de Carbohidratos , Humanos , Isomerismo , Células MCF-7 , Ratones , Modelos Biológicos , Simulación de Dinámica Molecular , Mucina-1/química , Técnicas de Síntesis en Fase Sólida , Resonancia por Plasmón de SuperficieRESUMEN
Angiotensin-converting enzyme (ACE) inhibitors have non-hemodynamic, pleiotropic effects on the immune response. The effects of ACE inhibitors on the production of cytokines and T-cell functions are well established. However, little is known on the effects of these medicines on humoral response to foreign antigens. In this study, we investigated the effect of enalapril treatment on ovalbumin (OVA)-specific IgG1 and IgG2c production in mice determined by ELISA. Two groups of 8-week-old C57BL/6 females mice (3-4/group) were subcutaneously immunized with OVA (10 µg/animal) in presence of Alhydrogel (1 mg/mouse) and boosted at day 21. The mice were treated with enalapril (5 mg/kg daily, po) or were left without treatment for one month. The animals were bled from the orbital plexus on days 0, 7, 14, 21, and 28 after the first immunization and the sera were stored at -20°C until usage. OVA-specific serum IgG1 and IgG2c were determined by ELISA using serum from each individual animal. The results showed that enalapril significantly increased anti-OVA serum IgG2c in the secondary response without affecting IgG1 synthesis. These data expand our understanding on the properties of enalapril on the immune response, including antibody production.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Enalapril/farmacología , Inmunidad Humoral/efectos de los fármacos , Inmunoglobulina G/sangre , Ovalbúmina/inmunología , Animales , Formación de Anticuerpos/efectos de los fármacos , Femenino , Inmunoglobulina G/inmunología , Ratones Endogámicos C57BL , Modelos Animales , Células TH1/inmunología , Células Th2/inmunologíaRESUMEN
To evaluate the effect of supplementation with mannan oligosaccharides, avilamycin and halquinol, alone or in combination, on the performance, carcass characteristics and antibody production in broilers (1-49 days old), male broiler chicks (n=1440; Cobb 500; one day old) were housed and distributed into a completely randomized design into six treatments (eight replicates; 30 animals per pen). To produce the experimental diets, three types of performance enhancer additives were used. Halquinol (HAL), avilamycin (AVI) and mannan oligosaccharides (MOS) were included (alone or in combination) in the basal diet (instead of corn starch). Effects of diet were observed on results of animal performance in the period 1-21 and 1-42 days old. Broilers fed with a diet without growth promoter showed lower weight gain in relation to those fed with diets with antimicrobials, MOS or a combination of them. In the period 1-49 days old, feed conversion increased in broilers fed with rations without promoter. At the end of the experimental period no influence of diets was observed on the carcass yield and cuts, and titles of specific antibodies to avian infectious bronchitis. The use of MOS and/or antimicrobials (AVI or HAL), alone or in combination, improves feed conversion of broilers reared until 49 days of age.(AU)
Para avaliar o efeito da suplementação com mananoligossacarídeo, avilamicina e halquinol, isoladamente ou combinados, sobre o desempenho, características de carcaça e produção de anticorpos em frangos de corte (1-49 dias de idade), pintos machos de corte (n=1440; linhagem Cobb 500; idade: um dia) foram alojados e distribuídos em delineamento experimental inteiramente casualizado com seis tratamentos (oito repetições; 30 animais por unidade experimental). Para compor as rações experimentais, três tipos de aditivos melhoradores de desempenho foram usados. Halquinol (HAL), avilamicina (AVI) e mananoligossacarídeo (MOS) foram incluídos (isoladamente ou em associação) na ração basal (em substituição ao amido de milho). Foi observado efeito das rações sobre os resultados de desempenho dos animais no período 1-21 e 1-42 dias de idade. As aves alimentadas com ração sem melhorador de desempenho apresentaram menor ganho de peso em relação àquelas que consumiram rações com antimicrobianos, MOS ou uma combinação deles. No período 1-49 dias de idade, a conversão alimentar aumentou nas aves alimentadas sem melhorador de desempenho. No final do período experimental, não foi observado efeito das rações sobre o rendimento de carcaça e cortes e títulos de anticorpos específicos contra bronquite infecciosa aviária. A utilização de mananoligossacarídeo e/ou antimicrobianos (avilamicina e halquinol), isoladamente ou combinados, melhora a conversão alimentar de frangos de corte criados até 49 dias de idade.(AU)
Asunto(s)
Animales , Prebióticos/administración & dosificación , Antiinfecciosos/administración & dosificación , Formación de Anticuerpos/efectos de los fármacos , Aves de Corral , Alimentación Animal , Aumento de Peso , Aditivos AlimentariosRESUMEN
Angiotensin-converting enzyme (ACE) inhibitors have non-hemodynamic, pleiotropic effects on the immune response. The effects of ACE inhibitors on the production of cytokines and T-cell functions are well established. However, little is known on the effects of these medicines on humoral response to foreign antigens. In this study, we investigated the effect of enalapril treatment on ovalbumin (OVA)-specific IgG1 and IgG2c production in mice determined by ELISA. Two groups of 8-week-old C57BL/6 females mice (3–4/group) were subcutaneously immunized with OVA (10 μg/animal) in presence of Alhydrogel (1 mg/mouse) and boosted at day 21. The mice were treated with enalapril (5 mg/kg daily, po) or were left without treatment for one month. The animals were bled from the orbital plexus on days 0, 7, 14, 21, and 28 after the first immunization and the sera were stored at –20°C until usage. OVA-specific serum IgG1 and IgG2c were determined by ELISA using serum from each individual animal. The results showed that enalapril significantly increased anti-OVA serum IgG2c in the secondary response without affecting IgG1 synthesis. These data expand our understanding on the properties of enalapril on the immune response, including antibody production.
Asunto(s)
Animales , Femenino , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Enalapril/farmacología , Inmunidad Humoral/efectos de los fármacos , Inmunoglobulina G/sangre , Ovalbúmina/inmunología , Formación de Anticuerpos/efectos de los fármacos , Inmunoglobulina G/inmunología , Ratones Endogámicos C57BL , Modelos Animales , Células TH1/inmunología , Células Th2/inmunologíaRESUMEN
Los problemas éticos de las investigaciones sobre vacunas han crecido en las últimas décadas en frecuencia y magnitud debido a la posición dominante de la industria farmacéutica en el desarrollo de esos estudios. Las tradicionales cuestiones de seguridad y eficacia se han visto agravadas por el conflicto de intereses introducido por la competencia comercial en un mercado a escala global de miles de millones de dólares. La integridad profesional de los investigadores, la responsabilidad moral de los patrocinadores, y la regulación y control por parte de los Estados nacionales, se muestra cuestionada en varios ejemplos. Los resultados de estos cambios son las amenazas a la protección de los derechos de las personas incluidas en estas investigaciones y el discutible progreso que resulta para la salud pública.(AU)
The ethical problems in vaccine research have grown in frequency and magnitude in last decades, due to the dominant place of the pharmaceutical industry in the development of such studies. Traditional issues of security and efficacy have been aggravated by the conflicts of interests introduced by commercial competition in a global market worth billions of dollars. We present here a few examples in which the professional integrity of researchers, the moral responsibility of sponsors, and the public regulation and control by national States are put into question. The consequences of these changes represent serious threats to the rights of people included in these studies as well as disputable progress for public health.(AU)
Asunto(s)
Animales , Masculino , Ratones , Benzamidas/administración & dosificación , Inhibidores Enzimáticos/administración & dosificación , Poli(ADP-Ribosa) Polimerasas/inmunología , Estrés Psicológico/enzimología , Estrés Psicológico/inmunología , Análisis de Varianza , Formación de Anticuerpos/efectos de los fármacos , Corticosterona/sangre , Relación Dosis-Respuesta a Droga , Habituación Psicofisiológica/fisiología , Hemocianinas/inmunología , Ratones Endogámicos C57BL , Poli(ADP-Ribosa) Polimerasas/efectos de los fármacos , Distribución Aleatoria , Restricción Física/fisiología , Estrés Psicológico/sangreRESUMEN
Los problemas éticos de las investigaciones sobre vacunas han crecido en las últimas décadas en frecuencia y magnitud debido a la posición dominante de la industria farmacéutica en el desarrollo de esos estudios. Las tradicionales cuestiones de seguridad y eficacia se han visto agravadas por el conflicto de intereses introducido por la competencia comercial en un mercado a escala global de miles de millones de dólares. La integridad profesional de los investigadores, la responsabilidad moral de los patrocinadores, y la regulación y control por parte de los Estados nacionales, se muestra cuestionada en varios ejemplos. Los resultados de estos cambios son las amenazas a la protección de los derechos de las personas incluidas en estas investigaciones y el discutible progreso que resulta para la salud pública.
The ethical problems in vaccine research have grown in frequency and magnitude in last decades, due to the dominant place of the pharmaceutical industry in the development of such studies. Traditional issues of security and efficacy have been aggravated by the conflicts of interests introduced by commercial competition in a global market worth billions of dollars. We present here a few examples in which the professional integrity of researchers, the moral responsibility of sponsors, and the public regulation and control by national States are put into question. The consequences of these changes represent serious threats to the rights of people included in these studies as well as disputable progress for public health.
Asunto(s)
Animales , Masculino , Ratones , Benzamidas/administración & dosificación , Inhibidores Enzimáticos/administración & dosificación , Poli(ADP-Ribosa) Polimerasas/inmunología , Estrés Psicológico/enzimología , Estrés Psicológico/inmunología , Análisis de Varianza , Formación de Anticuerpos/efectos de los fármacos , Corticosterona/sangre , Relación Dosis-Respuesta a Droga , Habituación Psicofisiológica/fisiología , Hemocianinas/inmunología , Poli(ADP-Ribosa) Polimerasas/efectos de los fármacos , Distribución Aleatoria , Restricción Física/fisiología , Estrés Psicológico/sangreRESUMEN
INTRODUCTION: Gastric bypass is today the most frequently performed bariatric procedure,but, despite of it, several complications can occur with varied morbimortality. Probably all bariatric surgeons know these complications, but, as bariatric surgery continues to spread, general surgeon must be familiarized to it and its management. Gastric bypass complications can be divided into two groups: early and late complications, taking into account the two weeks period after the surgery. This paper will focus the early ones. METHOD: Literature review was carried out using Medline/PubMed, Cochrane Library, SciELO, and additional information on institutional sites of interest crossing the headings: gastric bypass AND complications; follow-up studies AND complications; postoperative complications AND anastomosis, Roux-en-Y; obesity AND postoperative complications. Search language was English. RESULTS: There were selected 26 studies that matched the headings. Early complications included: anastomotic or staple line leaks, gastrointestinal bleeding, intestinal obstruction and incorrect Roux limb reconstruction. CONCLUSION: Knowledge on strategies on how to reduce the risk and incidence of complications must be acquired, and every surgeon must be familiar with these complications in order to achieve an earlier recognition and perform the best intervention. .
INTRODUÇÃO: O bypass gástrico é hoje o procedimento bariátrico mais realizado, mas, apesar disso, várias complicações podem ocorrer com variada morbimortalidade. Provavelmente todos os cirurgiões bariátricos conhecem essas complicações, mas como a cirurgia bariátrica continua a se espalhar, o cirurgião geral deve estar familiarizado com essas complicações e seu manuseio. As complicações do bypass gástrico podem ser divididas em dois grupos: as precoces e tardias, tendo em conta o período de duas semanas após a operação. Este artigo irá focar as precoces. MÉTODO: Foi realizada revisão da literatura utilizando as bases Medline/PubMed, Cochrane Library, SciELO, e informações adicionais sobre sites institucionais de interesse cruzando os descritores: bypass gástrico AND complicações; seguimento AND complicações; complicações pós-operatórias AND anastomose, Roux-en-Y; obesidade AND complicações pós-operatórias. A língua usada para a busca foi o inglês. RESULTADOS: Foram selecionados 26 artigos que combinavam com os descritores. As complicações imediatas foram: fístula na linha de grampeamento, sangramento gastrointestinal, obstrução intestinal e reconstrução incorreta da alça em Roux. CONCLUSÃO: O conhecimento sobre as estratégias de como reduzir o risco e incidência das complicações deve ser adquirido ao longo do tempo, e cada cirurgião deve estar familiarizado com essas complicações, a fim de reconhecê-las precocemente e realizar a melhor intervenção. .
Asunto(s)
Animales , Femenino , Ratones , Linfocitos B/fisiología , Poli(ADP-Ribosa) Polimerasas/fisiología , Formación de Anticuerpos/efectos de los fármacos , Formación de Anticuerpos/genética , Apoptosis/genética , Apoptosis/inmunología , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Supervivencia Celular/genética , Inmunoglobulina A/inmunología , /farmacología , Ratones Noqueados , Familia de Multigenes , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/fisiología , Poli(ADP-Ribosa) Polimerasas/química , Poli(ADP-Ribosa) Polimerasas/genética , Poli(ADP-Ribosa) Polimerasas/metabolismo , Homología de SecuenciaRESUMEN
We tested whether diethylcarbamazine (DEC) or ivermectin (IVM), both antiparasitic drugs with reported immunomodulatory properties, were able to affect the immune system to potentiate host defense mechanisms and protect against actinomycetoma in a mouse model. Male BALB/c mice of 10-12 weeks of age were injected with either Nocardia brasiliensis or saline solution. Recorded were the effects of a treatment by DEC (6 mg/kg per os daily for one week) or IVM (200 µg/kg subcutaneously on days 1 and 3) on (i) the development of mycetoma lesion, (ii) the expression of reactive oxygen intermediates (ROI) by phagocytes, (iii) the proliferation index of lymphocytes and (iv) antibody production of IgG and IgM. After an initial lesion in all mice, DEC inhibited a full development and progression of actinomycetoma resulting in a reduced lesion size (p < 0.001). IVM had no inhibitory effect on the development of mycetoma. Furthermore, DEC treatment was associated with a significant enhancement of ROI expression (p < 0.05) by polymorphonuclear neutrophils at day 3 after infection. Lymphocyte proliferation in response to N. brasiliensis antigens and concanavalin A in DEC-treated group was higher than in non-treated group at day 21 and 28 postinfection (p < 0.01). Significant changes in antibody response were not observed. By all parameters tested, DEC was superior to IVM regarding immunostimulatory potency. In conclusion, DEC expressed an in vivo influence on the immune status during the infection by N. brasiliensis leading to retrogression of the mycetoma and increasing cellular immune responses. Our findings may indicate a potential use of DEC as a putative adjuvant in infectious disease or vaccination.
Asunto(s)
Antiparasitarios/administración & dosificación , Dietilcarbamazina/administración & dosificación , Ivermectina/administración & dosificación , Micetoma/tratamiento farmacológico , Neutrófilos/efectos de los fármacos , Nocardia/inmunología , Animales , Formación de Anticuerpos/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Humanos , Inmunomodulación , Activación de Linfocitos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Micetoma/inmunología , Neutrófilos/fisiología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Leptospiral immunoglobulin-like (Lig) proteins are of great interest due to their ability to act as mediators of pathogenesis, serodiagnostic antigens, and immunogens. Purified recombinant LigA protein is the most promising subunit vaccine candidate against leptospirosis reported to date, however, as purified proteins are weak immunogens the use of a potent adjuvant is essential for the success of LigA as a subunit vaccine. In the present study, we compared xanthan pv. pruni (strain 106), aluminium hydroxide (alhydrogel), and CpG ODN as adjuvants in a LigA subunit vaccine preparation. Xanthan gum is a high molecular weight extracellular polysaccharide produced by fermentation of Xanthomonas spp., a plant-pathogenic bacterium genus. Preparations containing xanthan induced a strong antibody response comparable to that observed when alhydrogel was used. Upon challenge with a virulent strain of L. interrogans serovar Copenhageni, significant protection (Fisher test, P < 0.05) was observed in 100%, 100%, and 67% of hamsters immunized with rLigANI-xanthan, LigA-CpG-xanthan, and rLigANI-alhydrogel, respectively. Furthermore, xanthan did not cause cytotoxicity in Chinese hamster ovary (CHO) cells in vitro. The use of xanthan as an adjuvant is a novel alternative for enhancing the immunogenicity of vaccines against leptospirosis and possibly against other pathogens.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Vacunas Bacterianas/inmunología , Leptospirosis/inmunología , Leptospirosis/prevención & control , Polisacáridos Bacterianos/inmunología , Vacunas de Subunidad/inmunología , Animales , Formación de Anticuerpos/efectos de los fármacos , Antígenos Bacterianos/inmunología , Células CHO , Muerte Celular/efectos de los fármacos , Cricetinae , Cricetulus , Modelos Animales de Enfermedad , Femenino , Humedad , Inmunidad Humoral/efectos de los fármacos , Inmunización , Leptospira interrogans/fisiología , Leptospirosis/microbiología , Mesocricetus , Nitrógeno/análisis , Polisacáridos Bacterianos/farmacología , Ácido Pirúvico/análisisRESUMEN
The adjuvanticity of aluminum hydroxide and calcium phosphate on the antibody response in mice towards the venom of the snake Bothrops asper was studied. It was found that, in vitro, most of the venom proteins are similarly adsorbed by both mineral salts, with the exception of some basic phospholipases A2, which are better adsorbed by calcium phosphate. After injection, the adjuvants promoted a slow release of the venom, as judged by the lack of acute toxicity when lethal doses of venom were administered to mice. Leukocyte recruitment induced by the venom was enhanced when it was adsorbed on both mineral salts; however, venom adsorbed on calcium phosphate induced a higher antibody response towards all tested HPLC fractions of the venom. On the other hand, co-precipitation of venom with calcium phosphate was the best strategy for increasing: (1) the capacity of the salt to couple venom proteins in vitro; (2) the venom ability to induce leukocyte recruitment; (3) phagocytosis by macrophages; and (4) a host antibody response. These findings suggest that the chemical nature is not the only one determining factor of the adjuvant activity of mineral salts.
Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Hidróxido de Aluminio/administración & dosificación , Bothrops/inmunología , Fosfatos de Calcio/administración & dosificación , Venenos de Crotálidos/metabolismo , Leucocitos/inmunología , Macrófagos/inmunología , Hidróxido de Aluminio/química , Animales , Formación de Anticuerpos/efectos de los fármacos , Antivenenos/biosíntesis , Fosfatos de Calcio/química , Movimiento Celular , Células Cultivadas , Venenos de Crotálidos/inmunología , Masculino , Ratones , Ratones Endogámicos , Fagocitosis , Unión ProteicaRESUMEN
Food allergy is a severe human disease with imminent risk of life. Cissampelos sympodialis (Menispermaceae) is a native Brazilian plant used in Brazilian folk medicine for the treatment of respiratory allergies. In this study the experimental model of food allergy induced by ovalbumin (OVA) was used to determine whether the alcoholic extract of the plant (AFL) and its alkaloids match a therapeutic approach for this disease. Animal weight, diarrhea, OVA-specific IgE levels, inflammatory cell and cytokine profiles, mucus production and proportion of T cells on the mesenteric lymph node (MLN) were evaluated. Warifteine (W) or methyl-warifteine (MW) alkaloids slightly improve diarrhea score independently of AFL and all treatments decreased the OVA-specific IgE levels. Stimulated mesenteric lymph node (MLN) cells in the presence of the alkaloids diminished the IL-12p70 levels independently of IFN-γ or IL-13 secretion. The alkaloids increased the number of Treg cells on MLN and reduced the number of eosinophils and mast cells as well as mucus production in the gut. Therefore, the alkaloids modulate the immune response in food allergy by increasing regulatory T cells in MLN independently of Th1 or Th2 profiles.
Asunto(s)
Alcaloides/administración & dosificación , Cissampelos/inmunología , Eosinófilos/efectos de los fármacos , Hipersensibilidad a los Alimentos/tratamiento farmacológico , Mastocitos/efectos de los fármacos , Fitoterapia/métodos , Subgrupos de Linfocitos T/efectos de los fármacos , Linfocitos T Reguladores/efectos de los fármacos , Alcaloides/uso terapéutico , Animales , Formación de Anticuerpos/efectos de los fármacos , Células Cultivadas , Citocinas/metabolismo , Modelos Animales de Enfermedad , Eosinófilos/inmunología , Femenino , Hipersensibilidad a los Alimentos/inmunología , Humanos , Inmunoglobulina E/sangre , Mastocitos/inmunología , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/inmunología , Extractos Vegetales , Subgrupos de Linfocitos T/inmunología , Linfocitos T Reguladores/inmunologíaRESUMEN
Neonates and nursing infants are special with regard to immune development and vulnerability to infectious diseases. Although breast-feeding is essential to modulate and prime immune defenses, vaccines (an interventional prophylaxis) are crucial to prevent and control infectious diseases. During nursing, the type of feeding influences infants' natural defenses (including gut colonization) and their response to vaccines, both through cell-mediated immunity and specific antibody production. Given the variety and combination of vaccine components (antigens and excipients, preservative thimerosal, and aluminum adjuvants) and route of administration, there is a need to examine the role of infant feeding practices in intended and nonintended outcomes of vaccination. Maternal factors related to milk constituents (nutrients and pollutants) and feeding practices can affect response to vaccines. Collectively, studies that compared type of feeding (or used breast-feeding-adjusted statistical models) showed significant influence on some vaccines taken during infancy. Nurslings deprived of the full benefit of breast-feeding could have altered immune responses affecting vaccine outcome. In the absence of studies elucidating neurodevelopment (including excitoxicity) and immunotoxicity issues, vaccination practices should promote and support breast-feeding.
Asunto(s)
Lactancia Materna , Desarrollo Infantil/fisiología , Enfermedades Transmisibles/inmunología , Control de Infecciones/métodos , Leche Humana/inmunología , Vacunas , Formación de Anticuerpos/efectos de los fármacos , Formación de Anticuerpos/inmunología , Contaminación de Medicamentos , Contaminantes Ambientales/efectos adversos , Interacciones Alimento-Droga/inmunología , Promoción de la Salud , Humanos , Inmunidad Celular/efectos de los fármacos , Inmunidad Celular/inmunología , Recién Nacido , Sistema Nervioso/crecimiento & desarrollo , Vacunación/métodos , Vacunas/clasificación , Vacunas/inmunología , Vacunas/farmacologíaRESUMEN
Prolonged survival of long-lived antibody-secreting cells in the BM has been implicated as a key component of long-term humoral immunity. The current study was designed to uncover the extrinsic signals required for the generation and maintenance of ASC in several niches (peritoneum, spleen and bone-marrow). Our results show that protein mixture of the Thalassophryne nattereri venom induced a chronic Th2 humoral response that is characterized by splenic hyperplasia with GC formation and venom retention by follicular DCs. Retention of B1a in the BM were observed. In the late phase (120d) of chronic venom-response the largest pool of ASC into the peritoneal cavity consisted of B220(neg)CD43(high) phenotype; the largest pool of ASC into spleen was constituted by B220 positive cells (B220(high) and B220(low)), whereas the largest pool of ASC into in the BM was constituted by the B220(high)CD43(low) phenotype; and finally, terminally differentiated cells (B220(neg)CD43(high)) were only maintained in the inflamed peritoneal cavity in late phase. After 120d a sustained production of cytokines (KC, IL-5, TNF-α, IL-6, IL-17A and IL-23) and leukocytes recruitment (eosinophils, mast cells, and neutrophils) were induced. IL-5- and IL-17A-producing CD4+ CD44+ CD40L+ Ly6C+ effector memory T cells were also observed in peritoneal cavity. Finally, treatment of venom-mice with anti-IL-5- and anti-IL17A-neutralizing mAbs abolished the synthesis of specific IgE, without modifying the splenic hyperplasia or GC formation. In addition, IL-5 and IL-17A negatively regulated the expansion of B1a in peritoneal cavity and BM, and promoted the differentiation of these cells in spleen. And more, IL-5 and IL-17A are sufficient for the generation of ASC B220(neg) in the peritoneal cavity and negatively regulate the number of ASC B220(pos), confirming that the hierarchical process of ASC differentiation triggered by venom needs the signal derived from IL-5 and IL-17A.
Asunto(s)
Células Productoras de Anticuerpos/inmunología , Células Productoras de Anticuerpos/patología , Diferenciación Celular/inmunología , Inmunoglobulina E/inmunología , Inflamación/patología , Interleucina-17/inmunología , Interleucina-5/inmunología , Animales , Formación de Anticuerpos/efectos de los fármacos , Especificidad de Anticuerpos/efectos de los fármacos , Especificidad de Anticuerpos/inmunología , Antígenos/inmunología , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/inmunología , Células de la Médula Ósea/patología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Inmunidad Humoral/efectos de los fármacos , Inmunoglobulina E/biosíntesis , Memoria Inmunológica/efectos de los fármacos , Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Masculino , Toxinas Marinas/toxicidad , Ratones , Ratones Endogámicos BALB C , Especificidad de Órganos/efectos de los fármacos , Cavidad Peritoneal/patología , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/patología , Células Th2/efectos de los fármacos , Células Th2/inmunología , Factores de TiempoRESUMEN
The aim of this study was to determine the value of detoxified Shiga toxins Stx1 and Stx2 (toxoids of Escherichia coli) as mucosal adjuvants in neonatal mice for immunogenicity against the outer membrane proteins (OMPs) of Neisseria meningitidis B. Mucosal immunization has been shown to be effective for the induction of antigen-specific immune responses in both the systemic and mucosal compartments. Systemic antibody levels (IgG, IgG1, IgG2a, IgG2b, IgM, and IgA) and mucosal IgM and IgA were measured by ELISA using an N. meningitidis as an antigen. In addition, IFN-γ and IL-6 production were measured after stimulated proliferation of immune cells. Intranasal administration elicited a higher anti-OMP IgA response in both saliva and vaginal fluids. Our results suggest that both Stx1 and Stx2 toxoids are effective mucosal adjuvants for the induction of Ag-specific IgG, IgM, and IgA antibodies. The toxoids significantly enhanced the IgG and IgM response against OMPs with a potency equivalent to CT, with the response being characterized by both IgG1 and IgG2a isotypes, and increased IFN-gamma production. Additionally, bactericidal activity was induced with IgG and IgM antibodies of high avidity. These results support the use of the new toxoids as potent inducing adjuvants that are particularly suitable for mucosal immunization.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Inmunidad Mucosa , Neisseria meningitidis/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Administración Intranasal , Animales , Animales Recién Nacidos , Formación de Anticuerpos/efectos de los fármacos , Proliferación Celular , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Interferón gamma/biosíntesis , Interleucina-6/biosíntesis , Ratones , Ratones Endogámicos BALB C , Bazo/citologíaRESUMEN
This study is the first in the literature to focus attention on the possible immunotoxic effect of integerrimine N-oxide content in the butanolic residue (BR) of Senecio brasiliensis, a poisonous hepatotoxic plant that contains pyrrolizidine alkaloids (PAs). PAs have been reported as a pasture and food contaminant and as herbal medicine used worldwide and are responsible for poisoning events in livestock and human beings. After the plant extraction, BR extracted from Senecio brasiliensis was found to contain approximately 70% integerrimine N-oxide by elemental and spectral analyses ((1)H and (13)C NMR), which was administered to adult male Wistar Hannover rats at doses of 3, 6 and 9 mg/kg for 28 days. Body weight gain, food consumption, lymphoid organs, neutrophil analysis, humoural immune response, cellular immune response and lymphocyte analysis were evaluated. Our study showed that integerrimine N-oxide could promote an impairment in the body weight gain, interference with blood cell counts and a reducing T cell proliferative activity in rats; however, no differences in the neutrophil activities, lymphocytes phenotyping and humoural and cellular immune responses were observed. It is concluded that doses of integerrimine N-oxide here employed did not produce marked immunotoxic effects.
Asunto(s)
Formación de Anticuerpos/efectos de los fármacos , Inmunidad Celular/efectos de los fármacos , Tejido Linfoide/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Extractos Vegetales/farmacología , Alcaloides de Pirrolicidina/farmacología , Senecio/química , Animales , Ciclo Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Masculino , Neutrófilos/citología , Ratas , Ratas WistarRESUMEN
A 28 year-old female without history of previous disease. In the seventh month of her first pregnancy she developed hemorrhagic tendency that worsened in the early postpartum period. Activated partial thromboplastin time was 110 sec (control=35.8 sec) with negative tests for lupus anticoagulant. Factor VIII was <1% and a factor VIII inhibitor titer was 84 Bethesda Units/mL (BU). Initial therapy included methylprednisolone, prednisone, and cyclophosphamide. After two weeks of treatment, clinical conditions of the patient improved slightly and she was discharged. Outpatient therapy included azathioprine, and prednisone for a period of 22 months but in-hospital management was several times required. We initiated rituximab 375 mg/m2/week/4 weeks. A clinical improvement and increased levels of factors VIII and XI were observed 10 weeks later and factor VIII inhibitor decreased to undetectable levels. After a 82-month follow-up period (since the first rituximab infusion), she is asymptomatic and factor VIII and factor XI plasma levels are 70% and 94%, respectively FVIII inhibitor level is still undetectable. Rituximab seems an alternative for the treatment of acquired hemophilia refractory to standard treatment.