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Chinese Journal of Biotechnology ; (12): 4036-4046, 2021.
Article in Chinese | WPRIM | ID: wpr-921484


N-glycosylation modification, one of the most common protein post-translational modifications, occurs in heat shock protein gp96. The purpose of this study is to investigate the effect of N-glycosylation modification on immunologic function of the recombinant gp96 using the mutant gp96 in N-glycosylation sites. Firstly, wild-type and mutant gp96 proteins were expressed by insect expression system and their glycosylation levels were detected. To determine the effect of N-glycosylation on gp96 antigen presentation function, the IFN-γ+ CD8+ T cells in gp96-immunized mice and secretion level of IFN-γ were examined by flow cytometry and ELISA. The ATPase activity of gp96 was further detected by the ATPase kit. Finally, the effect of N-glycosylation on adjuvant function of gp96 for influenza vaccine was investigated in immunized mice. It was found that total sugar content of mutant recombinant gp96 was reduced by 27.8%. Compared to the wild type recombinant gp96, mutations in N-glycosylation sites resulted in decreased antigen presentation ability and ATPase activity of gp96. Furthermore, influenza vaccine-specific T cell levels induced by mutant gp96 as adjuvant were dramatically reduced compared to those by wild type recombinant gp96. These results demonstrate that N-glycosylation modification is involved in regulation of ATPase activity and antigen presentation function of gp96, thereby affecting its adjuvant function. The results provide the technical bases for development of gp96- adjuvanted vaccines.

Adjuvants, Immunologic , Animals , CD8-Positive T-Lymphocytes/metabolism , Glycosylation , Heat-Shock Proteins , Influenza Vaccines , Mice
Chinese Journal of Oncology ; (12): 1027-1033, 2021.
Article in Chinese | WPRIM | ID: wpr-920984


Bladder cancer is one of the common malignant tumors in China, with 75% of bladder cancer being non-muscle invasion with a high recurrence rate after surgery. Intravesical therapy is an useful methods to either directly kill tumor cells by infusing cytotoxic drugs into the bladder or directly or indirectly induce local immune responses of the body through infusing immune agents, such as bacillus calmette guerin, and thus reduce the risk of tumor recurrence and progression. In 2019, the Urological Chinese Oncology Group issued the "Expert consensus on intravesical therapy on non-muscle invasive bladder cancer" . Recently, great progress in the clinical diagnosis and treatment of non-muscle invasive bladder cancer has been achieved domestically and abroad, including the risk assessment of non-muscle invasive bladder cancer, the therapeutic choice of intravesical drugs, the adverse reactions and treatment experience of intravesical therapy, and clinical research on new types of intravesical drugs. This consensus is made according to domestic and overseas evidence-based medicine in combination with current clinical practice and experience of intravesical therapy for non-muscle invasive bladder cancer in China. It is an update of the 2019 expert consensus, with the wish to provide a guidance for domestic clinical standardized intravesical therapy for non-muscle invasive bladder cancer.

Adjuvants, Immunologic/therapeutic use , Administration, Intravesical , Consensus , Humans , Neoplasm Invasiveness , Neoplasm Recurrence, Local/drug therapy , Urinary Bladder Neoplasms/drug therapy
Article in Chinese | WPRIM | ID: wpr-878544


In recent years, the development of new vaccines such as nucleic acid vaccines, genetically engineered vaccines, and synthetic peptide vaccines has achieved rapid development. However, compared with traditional inactivated or live vaccines, these vaccines often have problems such as poor immunogenicity. Therefore, an adjuvant is needed to enhance its effect, and adjuvants have proven to be a key component in vaccines. There are many types of adjuvants, while currently no unified standard for the classification. At present, the most commonly used adjuvants are Aluminum adjuvant and Freund's adjuvant, but new generation vaccines will probably need new generation adjuvants. Thus, this review aims to showcase the current status of immune adjuvants, with the focus on immunomodulatory molecular adjuvant, antigen delivery adjuvant and compound adjuvant. This review provides new insights for the development of novel vaccine adjuvants.

Adjuvants, Immunologic/pharmacology , Freund's Adjuvant , Vaccines , Vaccines, Subunit
Arq. bras. med. vet. zootec. (Online) ; 72(5): 1805-1812, Sept.-Oct. 2020. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1131556


The objective of this study was to evaluate the effects of dietary supplementation with different doses of Curcuma longa hydrolate on the hematological, immunological and zootechnical parameters of Nile tilapia cultivated in a recirculation system (RAS). Nile tilapia (Oreochromis niloticus) were used, distributed in 16 polyethylene boxes, divided into four treatments: 0.0%; 2.5%; 7.5% and 10.0% of Curcuma longa hydrolate, in quadruplicate. After 45 days of treatment, four fish per experimental unit were anesthetized to remove blood aliquot for hematological and immunological analyzes and dissect the liver to evaluate the hepatosomatic index and final biometry. In the haematological analysis, the fish fed with 2.5% had a higher number of leukocytes, monocytes and lymphocytes than control, while the doses of 7.5% and 10.0% did not differ. Antimicrobial activity showed a significant decrease as the dose of C. longa hydrolate increased. The other hematological, immunological, hepatosomatic index and zootechnical data did not differ between treatments. Thus, supplementation of the hydrolate of Curcuma longa at a dosage of 2.5%, improved and maintained blood-immune homeostasis parameters in these animals, being suggested for further studies.(AU)

O objetivo deste estudo foi avaliar os efeitos da suplementação dietética com diferentes doses de hidrolato de Curcuma longa nos parâmetros hematológicos, imunológicos e zootécnicos da tilápia-do-nilo cultivada em sistema de recirculação. Utilizou-se tilápia- do-nilo (Oreochromis niloticus), distribuída em 16 caixas de polietileno, divididas em quatro tratamentos: 0,0%; 2,5%7,5% e 10,0% de hidrolato de Curcuma longa, em quadruplicata. Após 45 dias de tratamento, quatro peixes por unidade experimental foram anestesiados para remover uma alíquota sanguínea para análises hematológicas e imunológicas, e removeu-se o fígado para avaliar o índice hepatossomático e a biometria final. Na análise hematológica, os peixes alimentados com 2,5% apresentaram maior número de leucócitos, monócitos e linfócitos que no controle, enquanto as doses de 7,5% e 10,0% não diferiram. Por outro lado, a atividade antimicrobiana apresentou uma redução significativa à medida que a dose de hidrolato de C. longa aumentou. Os demais dados hematológicos, imunológicos, hepatossomáticos e zootécnicos não diferiram entre os tratamentos. Assim, a suplementação do hidrolato de Curcuma longa, na dose de 2,5%, melhorou os parâmetros hematoimunológicos e manteve a homeostase nesses animais, sendo sugerida para novos estudos.(AU)

Animals , Dietary Supplements/analysis , Curcumin/administration & dosage , Cichlids/immunology , Adjuvants, Immunologic/therapeutic use , Phytotherapy/veterinary
Rev. Méd. Clín. Condes ; 31(3/4): 343-351, mayo.-ago. 2020. tab
Article in Spanish | LILACS | ID: biblio-1223773


La vacunación es el medio más efectivo para controlar la morbilidad y mortalidad relacionadas con enfermedades infecciosas. Para lograr esto, necesitamos vacunas inmunogénicas y seguras que faciliten y mejoren sus condiciones de transporte, almacenamiento y administración. Gracias a los avances en inmunología y bioinformática, es posible impulsar el descubrimiento de nuevas vacunas para enfrentar la tuberculosis, el virus respiratorio sincicial, el Streptococcus agalactiae, la enfermedad meningocócica invasora, entre otros. Así también, nuevas tecnologías, como la producción de vacunas utilizando plantas transgénicas y parches de microagujas, los cuales podrían facilitar la producción, disminuir los costos y efectos adversos. Sin embargo, no solo necesitamos las vacunas, sino que debemos conocer la epidemiología de las enfermedades prevenibles con vacuna para tomar decisiones fundadas, con el objetivo de planificar estrategias sanitarias, medir su impacto y evaluar la seguridad de su utilización, para alcanzar las metas de salud pública y la confianza de la población.

Vaccination is the most effective strategy to avoid morbidity and mortality related to infectious diseases. To achieve this, we need immunogenic and safe vaccines that facilitate and improve its transport, storage and administration conditions. Thanks to current advances in immunology and bioinformatics, it is possible to boost the discovery of new vaccines to deal with tuberculosis, the respiratory syncytial virus, Streptococcus agalactiae, meningococcal invasive disease, among others. In addition to new technologies such as the production of plant-based vaccines, and microneedles patches, which can facilitate its production, reducing costs and adverse effects. However, vaccines is not the only thing that we need, because we must know the epidemiology and burden of disease to take informed decisions to design optimal strategies, measuring their impact and assessing the safety of their use in order to achieve the goals health and population confidence.

Humans , Vaccines/administration & dosage , Communicable Disease Control/methods , Vaccination/trends , Health Priorities , Streptococcal Infections/prevention & control , Adjuvants, Immunologic , Immunization/trends , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus Vaccines/administration & dosage , Tuberculosis Vaccines/administration & dosage , Decision , Meningococcal Infections/prevention & control
Braz. j. med. biol. res ; 53(8): e9886, 2020. tab
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1132547


The objective of this study was to compare the safety and efficacy of 0.2% hyaluronic acid (HA) topical gel and dexamethasone topical ointment in the treatment of recurrent aphthous ulcers (RAU) in children. This retrospective observational study included 104 patients who had more than two episodes of oral aphthous ulcers per year and were treated with HA (n=52) or dexamethasone (n=52) from August 15, 2014 to September 3, 2018. Therapy efficacy was evaluated based on the ulcer size and pain score before versus 7 days after either therapy. The paired t-test, chi-squared test, and independent t-test were utilized for statistical analyses. There was no significant difference in ulcer size or pain score between the HA and dexamethasone groups, on day 1 or day 7. Both treatments were tolerated well and no side effects were reported. No significant differences in body temperature, respiration rate, pulse, or systolic/diastolic blood pressure were observed between the start (day 1) and end of treatment (day 7), for either treatment. HA and dexamethasone showed similar efficacy in reducing ulcer size and pain scores, and were tolerated equally well in children with RAU. Future high-quality studies with larger numbers of patients are needed to confirm our findings.

Humans , Male , Female , Child , Stomatitis, Aphthous/drug therapy , Dexamethasone/therapeutic use , Adjuvants, Immunologic/therapeutic use , Hyaluronic Acid/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Pain , Recurrence , Retrospective Studies
Chinese Journal of Biotechnology ; (12): 1378-1385, 2020.
Article in Chinese | WPRIM | ID: wpr-826839


Listeria monocytogenes (Lm) is zoonotic pathogen that can cause listeriosis, and vaccine is one of the effective methods to prevent this pathogen infection. In this study, we developed a novel vaccine that is a mixture of inactivated bacteria and Montanide™ ISA 61 VG, a mineral oil adjuvant, and evaluated the safety and immune response characteristics of this vaccine. The mice immunized with the ISA 61 VG adjuvant had high safety, and it could induce significantly higher titer of anti-listeriolysin O (LLO) antibody and higher value of IgG2a/IgG1 ratio compared with the group without the adjuvant. In particular, it could provide 100% immune protection against lethal doses of Lm challenge in mice. In summary, ISA 61VG adjuvant significantly enhanced the ability of inactivated listeria vaccine to induce humoral and cellular immune responses, thereby enhanced the protective immune response in the host, and it is a potential vaccine candidate for the prevention of Lm infection in humans and animals.

Adjuvants, Immunologic , Pharmacology , Animals , Hemolysin Proteins , Allergy and Immunology , Pharmacology , Immunity, Cellular , Listeria monocytogenes , Allergy and Immunology , Listeriosis , Mice , Mice, Inbred BALB C , Vaccines, Inactivated , Allergy and Immunology
Braz. arch. biol. technol ; 63: e20190090, 2020. graf
Article in English | LILACS | ID: biblio-1132173


Abstract DNA vaccines have been evaluated as an option to prevent several diseases. In this study, the capacity of the xanthan biopolymer to improve the DNA vaccines immune response, administered intramuscularly, was evaluated. The experimental vaccines consisted of genes encoding fragments of the proteins LigA and LigB of Leptospira interrogans serogroup Icterohaemorrhagiae serovar Copenhageni strain Fiocruz L1-130. The humoral immune response was evaluated by indirect ELISA. Cytokine expression levels were determined by RT-qPCR. Compared to the control group, the IgG antibody levels of animals immunized with pTARGET/ligAni and pTARGET/ligBrep plasmids associated with xanthan biopolymer were significantly higher than the control group. Additionally, there was a significant increase in IL-17 expression in animals vaccinated with pTARGET/ligBrep and xanthan.

Animals , Female , Mice , Polysaccharides, Bacterial , DNA, Recombinant/pharmacology , Adjuvants, Immunologic/pharmacology , Xanthomonas campestris , Vaccines, DNA/pharmacology , Biopolymers/pharmacology , Enzyme-Linked Immunosorbent Assay , Leptospira interrogans serovar icterohaemorrhagiae , Antibodies
Biol. Res ; 53: 48, 2020. graf
Article in English | LILACS | ID: biblio-1142415


BACKGROUND: Psoriasis is a common chronic inflammatory skin disease. Keratinocytes hyperproliferation and excessive inflammatory response contribute to psoriasis pathogenesis. The agents able to attenuate keratinocytes hyper-proliferation and excessive inflammatory response are considered to be potentially useful for psoriasis treatment. Daphnetin exhibits broad bioactivities including anti-proliferation and anti-inflammatory. This study aims to evaluate the anti-psoriatic potential of daphnetin in vitro and in vivo, and explore underlying mechanisms. METHODS: HaCaT keratinocytes was stimulated with the mixture of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) to establish psoriatic keratinocyte model in vitro. Cell viability was measured using Cell Counting Kit-8 (CCK-8). Quantitative Real-Time PCR (qRT-PCR) was performed to measure the mRNA levels of hyperproliferative marker gene keratin 6 (KRT6), differentiation marker gene keratin 1 (KRT1) and inflammatory factors IL-1ß, IL-6, IL-8, TNF-α, IL-23A and MCP-1. Western blotting was used to detect the protein levels of p65 and p-p65. Indirect immunofluorescence assay (IFA) was carried out to detect p65 nuclear translocation. Imiquimod (IMQ) was used to construct psoriasis-like mouse model. Psoriasis severity (erythema, scaling) was scored based on Psoriasis Area Severity Index (PASI). Hematoxylin and eosin (H&E) staining was performed to examine histological change in skin lesion. The expression of inflammatory factors including IL-6, TNF-α, IL-23A and IL-17A in skin lesion was measured by qRT-PCR. RESULTS: Daphnetin attenuated M5-induced hyperproliferation in HaCaT keratinocytes. M5 stimulation significantly upregulated mRNA levels of IL-1ß, IL-6, IL-8, TNF-α, IL-23A and MCP-1. However, daphnetin treatment partially attenuated the upregulation of those inflammatory cytokines. Daphnetin was found to be able to inhibit p65 phosphorylation and nuclear translocation in HaCaT keratinocytes. In addition, daphnetin significantly ameliorate the severity of skin lesion (erythema, scaling and epidermal thickness, inflammatory cell infiltration) in IMQ-induced psoriasis-like mouse model. Daphnetin treatment attenuated IMQ-induced upregulation of inflammatory cytokines including IL-6, IL-23A and IL-17A in skin lesion of mice. CONCLUSIONS: Daphnetin was able to attenuate proliferation and inflammatory response induced by M5 in HaCaT keratinocytes through suppression of NF-κB signaling pathway. Daphnetin could ameliorate the severity of skin lesion and improve inflammation status in IMQ-induced psoriasis-like mouse model. Daphnetin could be an attractive candidate for future development as an anti-psoriatic agent.

Humans , Animals , Mice , Rabbits , Psoriasis/chemically induced , Psoriasis/drug therapy , Umbelliferones/pharmacology , Adjuvants, Immunologic/adverse effects , Imiquimod/adverse effects , Inflammation/drug therapy , Anti-Inflammatory Agents/pharmacology , Keratinocytes , Cell Proliferation , Mice, Inbred BALB C
Einstein (Säo Paulo) ; 18: eAO5262, 2020. tab
Article in English | LILACS | ID: biblio-1090059


ABSTRACT Objective To compare the frequency of respiratory tract infections in children treated with OM-85 BV and placebo during the 3-month therapy period, and observation for a further 3 months after treatment. Methods A randomized, double-blind, placebo-controlled trial was conducted with 54 children (6 months to 5 years old) with no past history of recurrent respiratory infections attending daycare center. Family members were instructed to administer one capsule per day for 10 consecutive days, for 3 months of OM-85 BV or placebo. Telephone interviews were conducted every 30 days. Results There was no significant difference in the number of respiratory infections between the groups. The mean number of respiratory tract infection in the OM-85 BV Group in the first 3 months was 0.92±0.87, and in the Placebo Group was 0.74±1.02, and at 6 months it was 1.62±1.47 and 1.03±1.34, respectively. Conclusion OM-85 BV was not effective in the primary prevention of respiratory tract infections. Although most authors recommend the use of this immunostimulant in children with a history of recurrent respiratory infections, more studies are needed to define its usefulness in the primary prevention of respiratory infections in healthy children exposed to few risk factors.

RESUMO Objetivo Comparar a frequência de infecções do trato respiratório em crianças tratadas com OM-85 BV e placebo durante o período de terapia de 3 meses, e observação por mais 3 meses após o tratamento. Métodos Foi realizado estudo randomizado, duplo-cego, controlado por placebo com 54 crianças (6 meses a 5 anos) sem história prévia de infecções respiratórias recorrentes, que frequentavam creches. Os membros da família foram instruídos a administrar uma cápsula por dia durante 10 dias consecutivos, durante 3 meses, de OM-85 BV ou placebo. Entrevistas telefônicas foram realizadas a cada 30 dias. Resultados Não houve diferença significativa no número de infecções respiratórias entre os grupos. O número médio de infecções do trato respiratório no Grupo OM-85 BV nos primeiros 3 meses foi de 0,92±0,87 e, no Grupo Placebo, de 0,74±1,02, e aos 6 meses foi de 1,62±1,47 e 1,03±1,34, respectivamente. Conclusão O OM-85 BV não foi eficaz na prevenção primária de infecções do trato respiratório. Embora a maioria dos autores recomende o uso deste imunoestimulante em crianças com história de infecções respiratórias recorrentes, mais estudos são necessários para definir sua utilidade na prevenção primária de infecções respiratórias em crianças saudáveis expostas a poucos fatores de risco.

Humans , Male , Female , Infant , Child, Preschool , Primary Prevention/methods , Cell Extracts/therapeutic use , Adjuvants, Immunologic/therapeutic use , Respiratory Tract Infections/drug therapy , Tobacco Smoke Pollution , Breast Feeding , Child Day Care Centers , Pilot Projects , Double-Blind Method , Treatment Outcome
Rev. chil. pediatr ; 90(6): 668-674, dic. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1058199


Resumen: Los pacientes con Inmunodeficiencias primarias (IDP) tienen un riesgo elevado de complicaciones severas por la vacuna BCG, incluso mortalidad. Es necesario evaluar periódicamente el riesgo versus beneficio de la vacunación universal BCG en el periodo neonatal. Chile es un país con baja incidencia de tuberculosis (TB) pero cuya epidemiología ha cambiado recientemente con un aumento de los casos. Cambios en esquemas de vacunación BCG en países con incidencias mayores o similares de TB y con coberturas de vacunación menores han sido posibles sin aumento de los casos graves de TB que son los que previene la BCG. El cambio ha evitado complicaciones graves en pacientes con IDP. Creemos que un análisis crítico de la fecha de vacunación BCG debe realizarse hoy en Chile. Más aún dada la posibilidad técnica de realizar screening neonatal de IDP.

Abstract: Patients with Primary Immunodeficiencies (PID) are at a higher risk of developing severe morbidities and mortality due to the administration of BCG vaccine. Risk-to-benefit of universal BCG vaccina tion of newborns must be assessed periodically. Chile has a low incidence of tuberculosis (TB) but the local epidemiology has recently changed with an increase of TB cases. Changes in the BCG vaccine schedule have been made in countries with similar or higher TB incidences and lower BCG vaccine coverage, with no increase in the severe TB cases, which are prevented by BCG. These changes have prevented serious complications in PID patients. We propose a critical analysis of the BCG adminis tration date in Chile due to the technical possibility of performing neonatal PID screening.

Humans , Infant, Newborn , Infant , BCG Vaccine/adverse effects , Adjuvants, Immunologic/adverse effects , Primary Immunodeficiency Diseases/complications , Tuberculosis/prevention & control , Tuberculosis/epidemiology , Chile/epidemiology , Incidence , Immunization Schedule , Severe Combined Immunodeficiency/complications , Hematopoietic Stem Cell Transplantation/mortality , Contraindications, Drug
Int. braz. j. urol ; 45(2): 315-324, Mar.-Apr. 2019. tab, graf
Article in English | LILACS | ID: biblio-1002193


ABSTRACT Objectives: To evaluate the neutrophil-to-lymphocyte ratio (NLR) as a prognostic factor for response of high risk non muscle invasive bladder cancer (HRNMIBC) treated with BCG therapy. Materials and Methods: Between March 2010 and February 2014 in a tertiary center 100 consecutive patients with newly diagnosed HRNMIBC were retrospectively analyzed. Patients were divided according to NLR value: 46 patients with NLR value less than 3 (NLR < 3 group), and 54 patients with NLR value more than 3 (NLR ≥ 3 group). At the end of follow-up 52 patients were high grade disease free (BCG-responder group) and 48 patients underwent radical cystectomy for high grade recurrence or progression to muscle invasive disease (BCG non-responder group). The average follow-up was 60 months. Intervention: analysis and correlation of preoperative NLR value with response to BCG in terms of recurrence and progression. Results: The optimal cut-off for NLR was ≥ 3 according to the receiver operating characteristics analysis (AUC 0.760, 95% CI, 0.669-0.850). Mean NLR value was 3.65 ± 1.16 in BCG non-responder group and 2.61 ± 0.77 in BCG responder group (p = 0.01). NLR correlated with recurrence (r = 0.55, p = 0.01) and progression risk scores (r = 0.49, p = 0.01). In multivariate analysis, NLR (p = 0.02) and EORTC recurrence risk groups (p = 0.01) were associated to the primary endpoint. The log-rank test showed statistically significant difference between NLR < 3 and NLR ≥ 3 curves (p < 0.05). Conclusions: NLR value preoperatively evaluated could be a useful tool to predict BCG response of HRNMIBC. These results could lead to the development of prospective studies to assess the real prognostic value of NLR in HRNMIBC.

Humans , Male , Female , Aged , Urinary Bladder Neoplasms/drug therapy , BCG Vaccine/therapeutic use , Lymphocytes/pathology , Carcinoma, Transitional Cell/drug therapy , Adjuvants, Immunologic/therapeutic use , Neutrophils/pathology , Prognosis , Urinary Bladder Neoplasms/surgery , Urinary Bladder Neoplasms/pathology , Carcinoma, Transitional Cell/surgery , Carcinoma, Transitional Cell/pathology , Biomarkers, Tumor/blood , Cystectomy , Retrospective Studies , Lymphocyte Count , Disease Progression , Neoplasm Grading , Middle Aged , Neoplasm Recurrence, Local/surgery , Neoplasm Staging
An. bras. dermatol ; 94(2): 221-223, Mar.-Apr. 2019. graf
Article in English | LILACS | ID: biblio-1001143


Abstract Vegetative chronic genital herpes is an atypical presentation of herpes simplex 2 that it is usually seen in patients coinfected with human immunodeficiency virus. Clinically, it is characterized by extensive ulcers that evolve to chronification and hypertrophic pseudotumor forms. Antiviral drugs are recommended for the treatment, and acyclovir is the most used one. Foscarnet is the treatment of choice to resistant cases, although treatment failure has been reported. We report a male patient, previously diagnosed with human immunodeficiency virus who developed vegetative chronic genital herpes resistant to acyclovir and successfully treated with imiquimod.

Humans , Male , Adult , Herpes Genitalis/drug therapy , Adjuvants, Immunologic/therapeutic use , AIDS-Related Opportunistic Infections/drug therapy , /therapeutic use , Herpes Genitalis/diagnosis , Adjuvants, Immunologic/administration & dosage , Chronic Disease , Treatment Outcome , Dose-Response Relationship, Drug , /administration & dosage
Rev. chil. enferm. respir ; 35(3): 219-224, 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1058077


Existen diversos lisados bacterianos, siendo OM-85 (Broncho-Vaxom®) el que posee mayor evidencia en cuanto a su rol inmunoprotector sobre infecciones respiratorias en población pediátrica. Sus mecanismos de acción producen efectos inmunomoduladores que potencialmente podrían prevenir el asma en etapas precoces de la vida, actuar sobre la disminución de crisis y ser un aporte a la terapia convencional del asma. Este artículo expone las principales evidencias en relación con estos compuestos, con enfoque en la actualidad y el desarrollo futuro, en especial sobre OM-85.

There are several bacterial lysates, being OM-85 (Broncho-Vaxom®) the one with the greatest evidence regarding its immunoprotective role on respiratory infections in the pediatric population. Its mechanisms of action produce immunomodulatory effects that could potentially prevent asthma in early stages of life, act on the reduction of crisis and be a contribution to conventional asthma therapy. This article shows the main evidences in relation to these compounds, the current focus and future development, especially on OM-85.

Humans , Respiratory Tract Infections/prevention & control , Asthma/drug therapy , Adjuvants, Immunologic/therapeutic use , Asthma/complications , Asthma/immunology , Anti-Bacterial Agents/therapeutic use
Rio de Janeiro; s.n; 2019. xxi, 150 p. ilus.
Thesis in Portuguese | LILACS | ID: biblio-1026458


A vacina de febre amarela atenuada é uma das mais bem-sucedidas já desenvolvidas. Entretanto, restrições de administração para pacientes imunodeprimidos e raros eventos adversos associados são desvantagens que motivam o desenvolvimento de vacinas mais seguras. À medida que aumenta a segurança, a imunogenicidade diminui na ausência de replicação viral. Nesse contexto, adjuvantes são elementos chave na ativação da imunidade inata para modulação das respostas adaptativas e proteção. Adjuvantes de diferentes naturezas e mecanismos de ação têm sido estudados: imunoestimuladores como agonistas de TLR, carreadores de antígenos e agentes de efeito depósito. Nesse estudo pretendemos identificar adjuvantes promissores para o desenvolvimento de novos candidatos vacinais para febre amarela. Para isso, camundongos C57BL/6 foram imunizados com diferentes formulações de antígenos modelo (vírus inativado e proteínas de envelope recombinantes produzidas em diferentes sistemas de expressão) com os adjuvantes: Al(OH)3; Addavax (emulsão baseada em esqualeno); combinações de Al(OH)3 e Flagelina FliC (agonista de TLR5); e CAF01 (nanopartícula) em esquema de 2 doses (D0 e D28) ou 3 doses (D0, D14 e D28). Após a imunização, os camundongos foram desafiados com inóculo letal do vírus de febre amarela por via intracerebral para determinar as taxas de sobrevivência. Os soros foram analisados por ELISA e PRNT50 para detecção dos títulos de IgG total e anticorpos neutralizantes

O vírus FA17DD inativado apresentou o melhor desempenho como antígeno modelo, sendo capaz de induzir 100% de proteção ao desafio após imunização com 2 doses na formulação com o adjuvante Addavax e 70% de proteção na formulação com hidróxido de alumínio. Os demais adjuvantes avaliados (Al(OH)3/ Flagelina FliC e CAF01) não foram capazes de gerar incremento de proteção com os antígenos avaliados. As formulações experimentais com melhor desempenho (FA17DD inativado/Addavax e FA17DD inativado/Al(OH3) foram avaliadas em um segundo ensaio para melhor caracterização das respostas imunológicas envolvidas na proteção. Ambas foram capazes de induzir apenas níveis basais de anticorpos neutralizantes; porém altos títulos de IgG para o vírus da febre amarela com predomínio do subtipo IgG1. A caracterização das respostas celulares locais (ELISpot citocinas e células B) no sítio de inoculação nos tempos pré e pós-desafio revelou níveis superiores de IFNγ nos animais sobreviventes. Após o desafio, todos os animais sobreviventes apresentaram altos títulos de anticorpos neutralizante e IgG total, com incremento do subtipo IgG2a. O uso de Addavax como adjuvante para vacinas não vivas para febre amarela surge como uma alternativa promissora de induzir proteção com menor número de doses. A aplicação do modelo de desafio murino para febre amarela na avaliação de novos adjuvantes se mostrou uma abordagem promissora para a avaliação de novos adjuvantes para uso neste modelo, bem como na geração de conhecimentos extrapoláveis para outros candidatos vacinais em desenvolvimento. (AU)

Animals , Biological Assay , Recombinant Proteins , Vaccines, Inactivated , Adjuvants, Immunologic , Yellow Fever Vaccine
Braz. arch. biol. technol ; 62: e19170811, 2019. tab, graf
Article in English | LILACS | ID: biblio-1039131


Abstract Stress in intensive fish farming hamper immune function of fish and cause losses by disease outbreaks, a situation that can be minimized, but cannot be completely circumvented, by the use of immunomodulators. Addition of immunomodulators to aquafeeds has thus become a common practice. β-glucan (BG) is one of most studied and effective immunomodulators, aquaculture purposes included. Extracted from cell walls of bacteria, fungi and selected cereals, BG activity depends on the source and extraction methods. This study evaluated effects of two BG products (BG1 and BG2), extracted from Saccharomyces cerevisiae under varying extraction methods and with different immune activity, on the feeding of pacu Piaractus mesopotamicus juveniles. BG1 provided higher leukocytes respiratory activity when fed at 0.5% inclusion for 10 days and 0.1% inclusion for 15 days. Both products seems to cause negative effect on lysozyme concentration and monocytes profile when fed to pacu for 15 days at 0.5% inclusion. Although the results for BG2 did not differ from control (diet devoid of BG), the proximity with the BG1 behavior is a indicative that a commercial product with smaller BG concentration can be effective when more refined technology is used in extraction process.

Adjuvants, Immunologic , Aquaculture , Muramidase , Aeromonas hydrophila , Leukocytes
Einstein (Säo Paulo) ; 17(4): eAO4637, 2019. tab, graf
Article in English | LILACS | ID: biblio-1019809


ABSTRACT Objective: To evaluate intervertebral disc levels of inflammatory factor (interleukin 6) and proteinase activity (cathepsin B) in patients with a degenerative disease and serum levels of interleukin 6, serum cathepsin B activity and hyaluronic acid biomarkers. Methods: We conducted immunohistochemistry studies of intervertebral discs to analyze interleukin 6 and cathepsin B levels of patients with degenerative disease and spine fracture (Control Group) and to measure hyaluronic acid, interleukin 6 and cathepsin B activity from sera of intervertebral disc degeneration patients, fracture patients, and healthy individuals. Results: Interleukin 6 and cathepsin B seem to be related with physiopathology of intervertebral disc degeneration, since the levels of both were higher in discs of patients with intervertebral disc degeneration. Interleukin 6 and cathepsin B do not represent good biomarkers of degenerative intervertebral disc disease, since the level of such compounds is increased in the plasma of patients with fractures. Conclusion: Hyaluronic acid can be a biomarker for intervertebral disc degeneration, because hyaluronic acid levels were higher only in sera of patients with intervertebral disc degeneration.

RESUMO Objetivo: Avaliar os níveis de fatores inflamatórios nos discos intervertebrais (interleucina 6) e proteinase (catepsina B) em pacientes com doença degenerativa de disco intervertebral, além de verificar os níveis séricos de interleucina 6, ácido hialurônico e atividade sérica da catepsina B. Métodos: Foi realizado exame imuno-histoquímica dos discos intervertebrais de pacientes com doença degenerativa e fratura da coluna (Grupo Controle) e análise do plasma de pacientes com doença degenerativa de disco intervertebral. Como controle, foram utilizados plasma de pacientes com fraturas, além de indivíduos saudáveis. Resultados: Interleucina 6 e catepsina B sugerem relação com a fisiopatologia da doença degenerativa de disco intervertebral, uma vez que os níveis de ambos foram maiores nos discos de pacientes com doença degenerativa de disco intervertebral. Interleucina 6 e catepsina B não representam bons biomarcadores da doença degenerativa do disco intervertebral, já que também encontram níveis aumentados em plasma de pacientes com fratura. Conclusão: O ácido hialurônico é um possível biomarcador de doença degenerativa de disco intervertebral, porque os níveis de ácido hialurônico foram maiores apenas em plasma de pacientes com doença degenerativa de disco intervertebral.

Humans , Male , Female , Adult , Cathepsin B/blood , Biomarkers/blood , Adjuvants, Immunologic/blood , Interleukin-6/blood , Intervertebral Disc Degeneration/diagnosis , Hyaluronic Acid/blood , Immunohistochemistry , Case-Control Studies , Prospective Studies , Analysis of Variance , Sensitivity and Specificity , Inflammation Mediators/blood , Intervertebral Disc Degeneration/physiopathology , Intervertebral Disc Degeneration/blood , Intervertebral Disc/physiopathology