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1.
Eur J Med Res ; 27(1): 6, 2022 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-35027080

RESUMEN

SARS-CoV-2, a novel coronavirus, is the agent responsible for the COVID-19 pandemic and is a major public health concern nowadays. The rapid and global spread of this coronavirus leads to an increase in hospitalizations and thousands of deaths in many countries. To date, great efforts have been made worldwide for the efficient management of this crisis, but there is still no effective and specific treatment for COVID-19. The primary therapies to treat the disease are antivirals, anti-inflammatories and respiratory therapy. In addition, antibody therapies currently have been a many active and essential part of SARS-CoV-2 infection treatment. Ongoing trials are proposed different therapeutic options including various drugs, convalescent plasma therapy, monoclonal antibodies, immunoglobulin therapy, and cell therapy. The present study summarized current evidence of these therapeutic approaches to assess their efficacy and safety for COVID-19 treatment. We tried to provide comprehensive information about the available potential therapeutic approaches against COVID-19 to support researchers and physicians in any current and future progress in treating COVID-19 patients.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19/terapia , Inmunización Pasiva , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Neutralizantes , Antivirales/uso terapéutico , Ensayos Clínicos como Asunto , Suplementos Dietéticos , Humanos , Inmunización Pasiva/métodos , Inmunoglobulinas Intravenosas/uso terapéutico , Pandemias , SARS-CoV-2 , Resultado del Tratamiento , Sueroterapia para COVID-19
2.
Theranostics ; 11(3): 1207-1231, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33391531

RESUMEN

Rationale: Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19. Methods: We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of in vitro, in vivo, and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020. Results: We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study. Through 12,200 title and 830 full-text screenings for COVID-19, eight in vitro studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated. There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19. Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461). Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), IFN-ß1b (n = 193), and convalescent plasma therapy (n = 126). Conclusions: This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence. Further RCTs are required.


Asunto(s)
Antivirales/uso terapéutico , COVID-19/terapia , Infecciones por Coronavirus/terapia , Síndrome Respiratorio Agudo Grave/terapia , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Animales , COVID-19/mortalidad , Carbamatos/uso terapéutico , Infecciones por Coronavirus/mortalidad , Modelos Animales de Enfermedad , Combinación de Medicamentos , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada/métodos , Humanos , Imidazoles/uso terapéutico , Inmunización Pasiva/métodos , Pirrolidinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Síndrome Respiratorio Agudo Grave/mortalidad , Sofosbuvir/uso terapéutico , Resultado del Tratamiento , Valina/análogos & derivados , Valina/uso terapéutico , Sueroterapia para COVID-19
3.
Ultrasound Obstet Gynecol ; 57(2): 195-203, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32959455

RESUMEN

In this review, we summarize evidence regarding the use of routine and investigational pharmacologic interventions for pregnant and lactating patients with coronavirus disease 2019 (COVID-19). Antenatal corticosteroids may be used routinely for fetal lung maturation between 24 and 34 weeks' gestation, but decisions in those with critical illness and those < 24 or > 34 weeks' gestation should be made on a case-by-case basis. Magnesium sulfate may be used for seizure prophylaxis and fetal neuroprotection, albeit cautiously in those with hypoxia and renal compromise. There are no contraindications to using low-dose aspirin to prevent placenta-mediated pregnancy complications when indicated. An algorithm for thromboprophylaxis in pregnant patients with COVID-19 is presented, which considers disease severity, timing of delivery in relation to disease onset, inpatient vs outpatient status, underlying comorbidities and contraindications to the use of anticoagulation. Nitrous oxide may be administered for labor analgesia while using appropriate personal protective equipment. Intravenous remifentanil patient-controlled analgesia should be used with caution in patients with respiratory depression. Liberal use of neuraxial labor analgesia may reduce the need for emergency general anesthesia which results in aerosolization. Short courses of non-steroidal anti-inflammatory drugs can be administered for postpartum analgesia, but opioids should be used with caution due to the risk of respiratory depression. For mechanically ventilated pregnant patients, neuromuscular blockade should be used for the shortest duration possible and reversal agents should be available on hand if delivery is imminent. To date, dexamethasone is the only proven and recommended experimental treatment for pregnant patients with COVID-19 who are mechanically ventilated or who require supplemental oxygen. Although hydroxycholoroquine, lopinavir/ritonavir and remdesivir may be used during pregnancy and lactation within the context of clinical trials, data from non-pregnant populations have not shown benefit. The role of monoclonal antibodies (tocilizumab), immunomodulators (tacrolimus), interferon, inhaled nitric oxide and convalescent plasma in pregnancy and lactation needs further evaluation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/virología , Atención Prenatal/métodos , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/terapia , COVID-19/virología , Ensayos Clínicos como Asunto , Femenino , Humanos , Inmunización Pasiva/métodos , Guías de Práctica Clínica como Asunto , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Sueroterapia para COVID-19
4.
Discov Med ; 29(158): 145-157, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33007190

RESUMEN

Coronavirus disease 2019 (COVID-19), a newly identified acute respiratory disease caused by a strain of novel coronavirus (SARS-CoV-2), has become a worldwide pandemic. From December 2019 to present, millions of cases have been reported, bringing unprecedented pressure on both health and epidemic prevention services in every country. As frontline healthcare workers, ophthalmologists face an increased threat of viral infection, not only because of close contact with patients during examinations or operations, but also due to evidence showing that ocular fluids such as tears or conjunctival secretions may carry the virus. The risk that healthcare workers face is emphasized by the loss of our colleagues who have sacrificed themselves in combating the virus. As a result, it is necessary to have a comprehensive understanding of the threats that we face. In the first part of this review, we start by explaining the structure of SARS-CoV-2 and examining its transmission and means of infection. Next, we summarize the latest scientific advancements of epidemiology, clinical presentations, and current treatments of COVID-19. In the second half of the review, we emphasize the ocular transmission, symptomatic manifestations, and the essential knowledge in an ophthalmology clinic setting. As the pandemic of COVID-19 continues to pose a threat to global health, we hope that this review makes a contribution to combating COVID-19.


Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/complicaciones , Oftalmopatías/virología , Neumonía Viral/complicaciones , Antivirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Betacoronavirus/inmunología , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/transmisión , Reposicionamiento de Medicamentos , Oftalmopatías/diagnóstico , Oftalmopatías/inmunología , Oftalmopatías/terapia , Humanos , Inmunización Pasiva/métodos , Factores Inmunológicos/uso terapéutico , Medicina Tradicional China/métodos , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Neumonía Viral/transmisión , SARS-CoV-2 , Sueroterapia para COVID-19
5.
Front Immunol ; 11: 1888, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32849647

RESUMEN

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes severe respiratory tract infections in humans (COVID-19), has become a global health concern. Currently, several vaccine candidates against SARS-CoV-2 are in clinical trials but approval of these vaccines is likely to take a long time before they are available for public use. In a previous report, the importance of passive immunity and how immunoglobulin (Ig)G collected from recovered coronavirus patients could help in the protection against COVID-19 and boost the immune system of new patients was reported. Passive immunity by immunoglobulin transfer is a concept employed by most mammals and bovine IgG has a role to play in human therapy. IgG is one of the major components of the immunological activity found in cow's milk and colostrum. Heterologous transfer of passive immunity associated with the consumption of bovine immune milk by humans has been investigated for decades for its immunological activity against infections. This short review focuses on passive immunity and how microfiltered raw immune milk or colostrum collected from cows vaccinated against SARS-CoV-2 could provide short-term protection against SARS-CoV-2 infection in humans and could be used as an option until a vaccine becomes commercially available.


Asunto(s)
Betacoronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/terapia , Ingestión de Líquidos/inmunología , Inmunización Pasiva/métodos , Leche/inmunología , Pandemias/prevención & control , Neumonía Viral/prevención & control , Neumonía Viral/terapia , Vacunación , Animales , Anticuerpos Antivirales/inmunología , COVID-19 , Bovinos , Calostro/inmunología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Femenino , Humanos , Inmunoglobulina G/inmunología , Neumonía Viral/inmunología , Neumonía Viral/virología , SARS-CoV-2 , Vacunas Virales/inmunología
6.
Radiologia (Engl Ed) ; 61(2): 134-142, 2019.
Artículo en Inglés, Español | MEDLINE | ID: mdl-30580817

RESUMEN

OBJECTIVE: In patients with oncologic disease, immunotherapy has become established as an alternative or complementary therapy to traditional treatment options (surgery, radiotherapy, and chemotherapy). Currently available immunotherapy modes can be divided into two types: passive and active. The active type strengthens the immune system's response to tumor cells by activating both humoral immunity and cell-mediated immunity, using the adaptive response. This article aims to analyze the radiologic patterns of the response to immunotherapy through immune-response-related criteria and to describe the main adverse effects associated with this treatment approach. CONCLUSION: Imaging tests play a fundamental role in the follow-up of oncologic patients and in the assessment of their response to treatment. Immunotherapy represents a challenge for radiologists both in the evaluation of the response to immunotherapy and in the detection of the adverse effects associated with this treatment approach.


Asunto(s)
Inmunoterapia/métodos , Neoplasias/terapia , Radiólogos , Enfermedades del Sistema Endocrino/diagnóstico por imagen , Enfermedades del Sistema Endocrino/etiología , Enfermedades Gastrointestinales/diagnóstico por imagen , Enfermedades Gastrointestinales/etiología , Humanos , Inmunización Pasiva/efectos adversos , Inmunización Pasiva/métodos , Inmunoterapia/efectos adversos , Enfermedades del Mediastino/diagnóstico por imagen , Enfermedades del Mediastino/etiología , Neoplasias/patología , Neumonía/diagnóstico por imagen , Neumonía/etiología , Resultado del Tratamiento , Carga Tumoral , Vacunación/efectos adversos , Vacunación/métodos
7.
Hum Vaccin Immunother ; 14(11): 2728-2736, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29985756

RESUMEN

The isolation of broadly neutralising antibodies against the influenza haemagglutinin has spurred investigation into their clinical potential, and has led to advances in influenza virus biology and universal influenza vaccine development. Studies in animal models have been invaluable for demonstrating the prophylactic and therapeutic efficacy of broadly neutralising antibodies, for comparisons with antiviral drugs used as the standard of care, and for defining their mechanism of action and potential role in providing protection from airborne infection.


Asunto(s)
Anticuerpos Antivirales/uso terapéutico , Inmunización Pasiva/métodos , Virus de la Influenza A/inmunología , Gripe Humana/terapia , Animales , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Neutralizantes/farmacología , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/farmacología , Protección Cruzada/efectos de los fármacos , Protección Cruzada/inmunología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Humanos , Ratones , Resultado del Tratamiento
8.
Arch Virol ; 163(9): 2327-2335, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29725899

RESUMEN

Passive immunity is critical for protection of neonatal piglets against porcine epidemic diarrhea virus (PEDV). Here, we investigated the immunogenicity of an orf virus (ORFV) vector expressing the full-length spike (S) protein of PEDV (ORFV-PEDV-S) in pregnant gilts and its ability to confer passive immunity and protection in piglets. Three doses of ORFV-PEDV-S were given to two groups of PEDV-negative pregnant gilts, with the last dose being administered two weeks prior to farrowing. One of the two groups immunized with the ORFV-PEDV-S recombinant virus was also exposed to live PEDV orally on day 31 post-immunization (pi). Antibody responses were assessed in serum, colostrum and milk of immunized gilts, and passive transfer of antibodies was evaluated in piglet sera. The protective efficacy of ORFV-PEDV-S was evaluated after challenge of the piglets with PEDV. PEDV-specific IgG, IgA and neutralizing antibody (NA) responses were detected in ORFV-PEDV-S-immunized and ORFV-PEDV-S-immunized/PEDV-exposed gilts. PEDV NA, IgG and IgA were detected in the serum of piglets born to immunized gilts, demonstrating the transfer of antibodies through colostrum and milk. Piglets born to immunized gilts showed reduced morbidity and a marked reduction in mortality after PEDV challenge in comparison to control piglets. Piglets born to gilts that received ORFV-PEDV-S and were exposed to live PEDV showed stronger NA responses and lower clinical scores when compared to piglets born to gilts immunized with ORFV-PEDV-S alone. These results demonstrate the potential of ORFV as a vaccine delivery platform capable of eliciting passive immunity against PEDV.


Asunto(s)
Anticuerpos Antivirales/sangre , Infecciones por Coronavirus/prevención & control , Inmunidad Materno-Adquirida , Virus del Orf/inmunología , Virus de la Diarrea Epidémica Porcina/inmunología , Glicoproteína de la Espiga del Coronavirus/administración & dosificación , Enfermedades de los Porcinos/prevención & control , Animales , Animales Recién Nacidos , Anticuerpos Neutralizantes/sangre , Calostro , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Femenino , Vectores Genéticos/administración & dosificación , Vectores Genéticos/química , Vectores Genéticos/inmunología , Inmunización Pasiva/métodos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Leche , Virus del Orf/genética , Virus de la Diarrea Epidémica Porcina/patogenicidad , Embarazo , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/inmunología , Porcinos , Enfermedades de los Porcinos/inmunología , Enfermedades de los Porcinos/virología
9.
J Invest Dermatol ; 138(6): 1260-1267, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29391250

RESUMEN

Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by autoantibodies to COL17. Currently, systemic corticosteroids are used as first-line treatments for BP; alternatively, intravenous administration of high-dose IgG (IVIG) has been shown to be effective for patients with steroid-resistant BP in clinical practice. However, the effect of IVIG on BP has not fully been investigated. To examine the effects and mechanisms of action of IVIG against BP, we performed IVIG experiments using two experimental BP mouse models. One is a passive-transfer BP model that reproduces subepidermal separation in neonatal mice by the passive transfer of IgGs against COL17, such as polyclonal or monoclonal mouse IgG or IgG from BP patients. The other is an active BP model that continuously develops a disease phenotype in adult mice. IVIG decreased pathogenic IgG and the disease scores in both models. Injected IVIG distributed throughout the dermis and the intercellular space of the lower epidermis. Notably, IVIG inhibited the increase of IL-6 in both models, possibly by suppressing the production of IL-6 by keratinocytes. These results suggest that the inhibitory effects of IVIG on BP are associated with the reduction of pathogenic IgG and the modulation of cytokine production.


Asunto(s)
Autoanticuerpos/sangre , Inmunoglobulina G/administración & dosificación , Inmunoglobulinas Intravenosas/administración & dosificación , Interleucina-6/sangre , Penfigoide Ampolloso/tratamiento farmacológico , Administración Intravenosa , Animales , Autoanticuerpos/inmunología , Autoantígenos/genética , Autoantígenos/inmunología , Línea Celular , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Humanos , Inmunización Pasiva/métodos , Interleucina-6/inmunología , Interleucina-6/metabolismo , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Queratinocitos/microbiología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Colágenos no Fibrilares/genética , Colágenos no Fibrilares/inmunología , Penfigoide Ampolloso/sangre , Penfigoide Ampolloso/inmunología , Índice de Severidad de la Enfermedad , Piel/inmunología , Trasplante de Piel/métodos , Resultado del Tratamiento , Colágeno Tipo XVII
10.
Int Orthop ; 42(2): 239-245, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29119297

RESUMEN

INTRODUCTION: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterised by a painful ulceration mimicking infection of the operative site. To this day, there is still no general agreement on the medical and surgical treatment of PG. This systematic review of the literature aims to summarise recent studies about post-operative PG in orthopaedic surgery to improve its medical and surgical management. METHOD: In April 2017, we carried out an exhaustive review of the literature in MEDLINE, PubMed and Cochrane databases. Key words were pyoderma gangrenosum, orthopaedic surgery, and surgical wound infection. We identified 183 articles. After excluding articles reporting idiopathic PG, cases secondary to non-orthopaedic surgery, and cases about other subtypes of dermatosis, 30 studies were identified. We only included articles reporting PG after orthopaedic or trauma surgery. RESULTS: Thirty-one cases of PG have been reported, 58% (18) of which were in women, whose mean age was 56.5 years. Clinical signs were constant, the most frequently affected site was lower limbs [77.4% (24)] and delay of symptom onset was two to 17 days. Systemic corticosteroid therapy was systematic, polyvalent immunoglobulins were used in two cases and immunosuppressive drugs in one. Negative pressure therapy was used in seven cases and hyperbaric oxygen in three. DISCUSSION: Delayed diagnosis leads to one or more surgical revisions, which could have been avoided by using early and adapted medical treatment. Early onset of a painful and infected ulcer at the operating site in a patient at risk of PG is an indicator that dermatologist advice is recommended before surgical debridement. Surgical revision, outside the inflammatory phase and/or covered by a systemic corticosteroid therapy, does not lead to PG relapse. LEVEL OF EVIDENCE: IV: Systematic revue of the literature.


Asunto(s)
Piodermia Gangrenosa/diagnóstico , Infección de la Herida Quirúrgica/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Glucocorticoides/uso terapéutico , Humanos , Oxigenoterapia Hiperbárica/métodos , Inmunización Pasiva/métodos , Persona de Mediana Edad , Terapia de Presión Negativa para Heridas/métodos , Ortopedia/estadística & datos numéricos , Periodo Posoperatorio , Piodermia Gangrenosa/etiología , Piodermia Gangrenosa/terapia , Traumatología/estadística & datos numéricos
11.
J Dairy Sci ; 100(10): 8438-8442, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28755946

RESUMEN

Previous data have demonstrated that refractometers can be used to estimate serum IgG, and that a cut-point of 7.8% Brix should be used to identify failure of passive transfer (FPT) in 1-d-old Holstein calves. The objective of the present study was to validate the use of refractometry to estimate serum IgG concentrations and evaluate FPT in Jersey calves. Blood samples (n = 97) were obtained from 1- to 3-d-old Jersey calves and centrifuged at 3,300 × g for 20 min at 25°C. Serum was analyzed for % Brix, total protein (TP), and refractive index (nD) using a Sper Scientific Digital Refractometer (model #300036, Sper Scientific, Scottsdale, AZ) within 12 h of sampling. Samples were then frozen and later analyzed in the laboratory for IgG by radial immunodiffusion. The mean serum IgG concentration for all calves was 23.7 mg/mL (SD = 12.5), with a range of 2.3 to 65.5 mg/mL. Mean serum % Brix was 8.9 (SD = 1.1; range 6.5 to 12.0). Serum % Brix was moderately correlated with IgG concentration (r = 0.77). Total protein and IgG were moderately correlated (r = 0.790). Regression was used to determine cut-points for approximately 10, 12, and 14 mg of IgG/mL and to determine the sensitivity and specificity of refractometry to identify FPT (serum IgG <10 mg/mL at 24 h of life). Brix cut-points analyzed were 7.1, 7.3, and 7.6%; TP cut-points were 4.6, 5.0, and 5.5 g/dL; and nD cut-points were 1.34332, 1.34271, and 1.3448, respectively, for 10, 12, and 14 mg of IgG/mL. The 7.3% Brix and 4.6 g/dL TP cut-points resulted in the greatest percentage of samples being correctly classified. These data suggest that digital refractometry is an acceptable and rapid method to estimate immunoglobulin G in Jersey calf serum.


Asunto(s)
Inmunidad Colectiva , Inmunización Pasiva/veterinaria , Inmunoglobulina G/sangre , Refractometría/veterinaria , Animales , Animales Recién Nacidos , Bovinos , Calostro , Congelación , Inmunización Pasiva/métodos , Inmunodifusión/métodos , Inmunodifusión/veterinaria , Refractometría/instrumentación , Sensibilidad y Especificidad
12.
PLoS One ; 10(8): e0133665, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26267898

RESUMEN

Noroviruses are a major cause of acute gastroenteritis, but no vaccines or therapeutic drugs are available. Llama-derived single chain antibody fragments (also called VHH) are small, recombinant monoclonal antibodies of 15 kDa with several advantages over conventional antibodies. The aim of this study was to generate recombinant monoclonal VHH specific for the two major norovirus (NoV) genogroups (GI and GII) in order to investigate their potential as immunotherapy for the treatment of NoV diarrhea. To accomplish this objective, two llamas were immunized with either GI.1 (Norwalk-1968) or GII.4 (MD2004) VLPs. After immunization, peripheral blood lymphocytes were collected and used to generate two VHH libraries. Using phage display technology, 10 VHH clones specific for GI.1, and 8 specific for GII.4 were selected for further characterization. All VHH recognized conformational epitopes in the P domain of the immunizing VP1 capsid protein, with the exception of one GII.4 VHH that recognized a linear P domain epitope. The GI.1 VHHs were highly specific for the immunizing GI.1 genotype, with only one VHH cross-reacting with GI.3 genotype. The GII.4 VHHs reacted with the immunizing GII.4 strain and showed a varying reactivity profile among different GII genotypes. One VHH specific for GI.1 and three specific for GII.4 could block the binding of homologous VLPs to synthetic HBGA carbohydrates, saliva, and pig gastric mucin, and in addition, could inhibit the hemagglutination of red blood cells by homologous VLPs. The ability of Nov-specific VHHs to perform well in these surrogate neutralization assays supports their further development as immunotherapy for NoV treatment and immunoprophylaxis.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Proteínas de la Cápside/inmunología , Diarrea/prevención & control , Gastroenteritis/prevención & control , Inmunización Pasiva/métodos , Anticuerpos de Cadena Única/inmunología , Animales , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/aislamiento & purificación , Especificidad de Anticuerpos , Camélidos del Nuevo Mundo , Proteínas de la Cápside/química , Proteínas de la Cápside/genética , Técnicas de Visualización de Superficie Celular , Diarrea/inmunología , Diarrea/virología , Mapeo Epitopo , Epítopos/química , Epítopos/inmunología , Gastroenteritis/inmunología , Gastroenteritis/virología , Biblioteca de Genes , Pruebas de Inhibición de Hemaglutinación , Humanos , Sueros Inmunes/química , Inmunización , Masculino , Norovirus/efectos de los fármacos , Norovirus/inmunología , Norovirus/patogenicidad , Unión Proteica , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Anticuerpos de Cadena Única/administración & dosificación , Anticuerpos de Cadena Única/genética , Anticuerpos de Cadena Única/aislamiento & purificación , Porcinos
13.
Appl Microbiol Biotechnol ; 99(14): 5985-96, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25794873

RESUMEN

Heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli (ETEC) is one of the major virulence factors for causing diarrhea in piglets, and LT is a strong immunogen. Thus, LT represents an important target for development of vaccines and diagnostic tests. In this study, bioinformatic tools were used to predict six antigenic B cell epitopes in the B subunit of LT protein (LTB) of ETEC strains. Then, seven antigenic B cell epitopes of LTB were identified by polyclonal antisera (polyclonal antibody (PAb)) using a set of LTB-derived peptides expressed as maltose-binding protein (MBP) fusion protein. In addition, one LTB-specific monoclonal antibody (MAb) was generated and defined its corresponding epitope as mentioned above. This MAb was able to specifically bind with native LT toxin and has no cross-reaction with LT-II (type II heat-labile enterotoxin), Stx1 (Shiga toxin I), Stx2 (Shiga toxin II), STa (heat-stable enterotoxin I), and STb (heat-stable enterotoxin II) toxins. Further, this MAb was able to interrupt LT toxin specific binding to GM1 receptor, indicating that the corresponding epitope is the specific binding region to GM1 receptor. Moreover, in vitro and in vivo assay showed that the MAb was able to neutralize the native LT toxin. Diarrheal suckling pigs challenged with LT-positive ETEC strain recovered when an enema with this purified MAb was administered. This study will provide the foundation for further studies about the interaction between LT toxin and GM1 receptor and about the developing of epitope-based vaccines and specific therapeutic agent.


Asunto(s)
Anticuerpos Antibacterianos/inmunología , Anticuerpos Neutralizantes/inmunología , Toxinas Bacterianas/inmunología , Enterotoxinas/inmunología , Epítopos de Linfocito B/inmunología , Proteínas de Escherichia coli/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/aislamiento & purificación , Toxinas Bacterianas/genética , Biología Computacional , Diarrea/terapia , Enema , Enterotoxinas/genética , Epítopos de Linfocito B/genética , Infecciones por Escherichia coli/terapia , Infecciones por Escherichia coli/veterinaria , Proteínas de Escherichia coli/genética , Inmunización Pasiva/métodos , Pruebas de Neutralización , Unión Proteica , Receptores de Superficie Celular/metabolismo , Porcinos , Enfermedades de los Porcinos/terapia , Resultado del Tratamiento
14.
Clin Vaccine Immunol ; 21(11): 1528-33, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25209558

RESUMEN

Influenza causes serious and sometimes fatal disease in individuals at risk due to advanced age or immunodeficiencies. Despite progress in the development of seasonal influenza vaccines, vaccine efficacy in elderly and immunocompromised individuals remains low. We recently developed a passive immunization strategy using an adeno-associated virus (AAV) vector to deliver a neutralizing anti-influenza antibody at the site of infection, the nasal airways. Here we show that young, old, and immunodeficient (severe combined immunodeficient [SCID]) mice that were treated intranasally with AAV9 vector expressing a modified version of the broadly neutralizing anti-influenza antibody FI6 were protected and exhibited no signs of disease following an intranasal challenge with the mouse-adapted H1N1 influenza strain A/Puerto Rico/8/1934(H1N1) (PR8) (Mt. Sinai strain). Nonvaccinated mice succumbed to the PR8 challenge due to severe weight loss. We propose that airway-directed AAV9 passive immunization against airborne infectious agents may be beneficial in elderly and immunocompromised patients, for whom there still exists an unmet need for effective vaccination against influenza.


Asunto(s)
Anticuerpos Antivirales/inmunología , Terapia Biológica/métodos , Dependovirus/crecimiento & desarrollo , Portadores de Fármacos/administración & dosificación , Inmunización Pasiva/métodos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Administración Intranasal , Animales , Anticuerpos Neutralizantes/genética , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/genética , Dependovirus/genética , Modelos Animales de Enfermedad , Femenino , Huésped Inmunocomprometido , Ratones Endogámicos BALB C , Ratones SCID , Análisis de Supervivencia , Resultado del Tratamiento
15.
Anaerobe ; 30: 210-9, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25079668

RESUMEN

The pathophysiology of Clostridium difficile infections (CDI) could be considered as a three-step process that takes place after disruption of the digestive microbiota by antibiotics: 1) germination of spores; 2) multiplication and persistence of C. difficile in the colonic niche thanks to colonization factors; 3) production of the two toxins TcdA and TcdB and for some strains an additional toxin, the binary toxin CDT. Different immunization strategies against C. difficile have been developed, first regarding the toxins. Immunization assays with colonization factors have followed, and allowed accumulation of new data concerning theirs functions and immunogenicity. Here, we present the toxins, the colonization factors and their use in passive and active immunizations to treat and/or to prevent C. difficile infections. The various experiments performed in animal models and the first clinical trials in humans are reported.


Asunto(s)
Clostridioides difficile/inmunología , Infecciones por Clostridium/prevención & control , Inmunización Pasiva/métodos , Vacunación/métodos , Animales , Ensayos Clínicos como Asunto , Infecciones por Clostridium/inmunología , Evaluación Preclínica de Medicamentos , Humanos
16.
J Vet Intern Med ; 28(5): 1602-5, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24986262

RESUMEN

BACKGROUND: Diarrhea because of Salmonella infection is a cause of neonatal calf diarrhea. The stimulation of passive immunity in the calf by vaccinating the dam for Salmonella has shown some success in previous studies; however, there are no data on the use of currently licensed vaccines in the United States. OBJECTIVE: To determine whether vaccinating cows at dry-off with a commercially available Salmonella bacterial extract would stimulate Salmonella-specific antibodies in the colostrum of cows at calving and whether these antibodies would be transferred to the calf. ANIMALS: Sixty Holstein cattle and 59 calves from a herd presumed to be naïve to Salmonella. METHODS: Prospective clinical trial. Thirty cows were vaccinated at dry-off with a Salmonella enterica serovar Newport bacterial extract and again 4 weeks later. An additional 30 cows received only saline. Calves fed fresh colostrum from their dam within 4 hours of birth had blood collected 24 hours later. RESULTS: Vaccinated cattle had increased Salmonella Newport antibody titers at calving in blood (P = .01) and colostrum (P = .011). Calves that received colostrum from vaccinated cattle also had significant increase in Salmonella antibodies (1.04 ± 0.03) as compared to calves born to unvaccinated cows (0.30 ± 0.02). CONCLUSIONS AND CLINICAL IMPORTANCE: The results indicate that the use of a commercially available Salmonella vaccine can stimulate antibodies that are passed on to the calf via colostral transfer. Further studies need to be done to determine whether these antibodies will offer protection against Salmonella challenge.


Asunto(s)
Enfermedades de los Bovinos/prevención & control , Inmunización Pasiva/veterinaria , Salmonelosis Animal/prevención & control , Vacunas contra la Salmonella/uso terapéutico , Animales , Animales Recién Nacidos/inmunología , Bovinos , Enfermedades de los Bovinos/inmunología , Enfermedades de los Bovinos/microbiología , Calostro/inmunología , Femenino , Inmunidad Materno-Adquirida/inmunología , Inmunización Pasiva/métodos , Embarazo , Salmonella/inmunología , Salmonelosis Animal/inmunología , Vacunas contra la Salmonella/inmunología , Vacunación/métodos , Vacunación/veterinaria
17.
Recent Pat Antiinfect Drug Discov ; 8(3): 161-97, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24215506

RESUMEN

The relentless rise in antibiotic resistance among pathogenic bacteria and fungi, coupled with the high susceptibility of burn wounds to infection, and the difficulty of systemically administered antibiotics to reach damaged tissue, taken together have made the development of novel topical antimicrobials for burn infections a fertile area of innovation for researchers and companies. We previously covered the existing patent literature in this area in 2010, but the notable progress made since then, has highlighted the need for an update to bring the reader up to date on recent developments. New patents in the areas of topically applied antibiotics and agents that can potentiate the action of existing antibiotics may extend their useful lifetime. Developments have also been made in biofilm-disrupting agents. Antimicrobial peptides are nature's way for many life forms to defend themselves against attack by pathogens. Silver has long been known to be a highly active antimicrobial but new inorganic metal derivatives based on bismuth, copper and gallium have emerged. Halogens such as chlorine and iodine can be delivered by novel technologies. A variety of topically applied antimicrobials include chitosan preparations, usnic acid, ceragenins and XF porphyrins. Natural product derived antimicrobials such as tannins and essential oils have also been studied. Novel techniques to deliver reactive oxygen species and nitric oxide in situ have been developed. Light-mediated techniques include photodynamic therapy, ultraviolet irradiation, blue light, low-level laser therapy and titania photocatalysis. Passive immunotherapy employs antibodies against pathogens and their virulence factors. Finally an interesting new area uses therapeutic microorganisms such as phages, probiotic bacteria and protozoa to combat infections.


Asunto(s)
Antiinfecciosos Locales/uso terapéutico , Bacteriófagos , Biopelículas , Quemaduras/complicaciones , Inmunización Pasiva/métodos , Patentes como Asunto , Fototerapia/métodos , Probióticos/uso terapéutico , Infección de Heridas/terapia , Humanos , Infección de Heridas/complicaciones
18.
Rev. cuba. pediatr ; 85(2): 230-241, abr.-jun. 2013.
Artículo en Español | LILACS | ID: lil-678135

RESUMEN

En la actualidad existen diversos productos farmacéuticos constituidos por inmunoglobulinas (fundamentalmente IgG), purificadas por diversos métodos, lo que implica que pueden ser administradas por diversas vías (intramuscular, intravenosa y subcutánea). Estos productos tienen un amplio espectro de indicaciones en diversas enfermedades. Las inmunoglobulinas son los efectores finales de la respuesta inmune humoral, por lo que sus indicaciones fundamentales incluyen la terapia de reemplazo en enfermedades que cursan con déficit en la producción de anticuerpos, las situaciones en que se necesita de manera inmediata la presencia de anticuerpos neutralizantes, como en las terapias posexposición, y en enfermedades que cursan con disrregulación de la respuesta inmune


There are presently several pharmaceuticals made up of immunoglobulines (fundamentally IgG) purified by several methods, which means that they can be administered by different routes (intramuscularly, intravenously and subcutaneously). These products have a wide spectrum of prescriptions for several diseases. The immunoglobulins are the final effectors of the humoral immune response, so their fundamental prescriptions cover replacement therapies in diseases with antibody production deficit, situations requiring immediate presence of neutralizing antibodies such as post-exposure therapies, and diseases with immune response deregulation


Asunto(s)
Humanos , Autoinmunidad/fisiología , Inmunización Pasiva/métodos , Inmunoglobulina G/uso terapéutico , Pediatría/ética , Terapia Biológica/métodos
19.
Rev. cuba. pediatr ; 85(2): 230-241, abr.-jun. 2013.
Artículo en Español | CUMED | ID: cum-56784

RESUMEN

En la actualidad existen diversos productos farmacéuticos constituidos por inmunoglobulinas (fundamentalmente IgG), purificadas por diversos métodos, lo que implica que pueden ser administradas por diversas vías (intramuscular, intravenosa y subcutánea). Estos productos tienen un amplio espectro de indicaciones en diversas enfermedades. Las inmunoglobulinas son los efectores finales de la respuesta inmune humoral, por lo que sus indicaciones fundamentales incluyen la terapia de reemplazo en enfermedades que cursan con déficit en la producción de anticuerpos, las situaciones en que se necesita de manera inmediata la presencia de anticuerpos neutralizantes, como en las terapias posexposición, y en enfermedades que cursan con disrregulación de la respuesta inmune(AU)


There are presently several pharmaceuticals made up of immunoglobulines (fundamentally IgG) purified by several methods, which means that they can be administered by different routes (intramuscularly, intravenously and subcutaneously). These products have a wide spectrum of prescriptions for several diseases. The immunoglobulins are the final effectors of the humoral immune response, so their fundamental prescriptions cover replacement therapies in diseases with antibody production deficit, situations requiring immediate presence of neutralizing antibodies such as post-exposure therapies, and diseases with immune response deregulation(AU)


Asunto(s)
Humanos , Inmunoglobulina G/uso terapéutico , Terapia Biológica/métodos , Inmunización Pasiva/métodos , Autoinmunidad/fisiología , Pediatría/ética
20.
Hum Vaccin Immunother ; 9(5): 1039-48, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23319156

RESUMEN

This commentary summarizes the laboratory investigations and clinical trials published recently involving per-oral application of IgY supplemented food for specific orogastrointestinal disease prevention and control purposes. The prolonged use and misuse of conventional antibacterial drugs has spawned antibiotic resistant microbes prompting scientists to search for other germ-killing options. In particular, the use of IgY as a novel mode of immunotherapy using oral chicken immunoglobulin (IgY) to confer passive immunity has gained much interest as an inexpensive non-antibiotic alternative for the prophylaxis and treatment of a wide variety of infectious diseases. The stability of IgY in the orogastrointestinal tract and its safety profile has been well-documented. IgY has been used in the treatment or prevention of dental caries, periodontitis and gingivitis, gastritis and gastric ulcer, oral thrush and infant rotavirus diarrhea. The recent clinical trials on IgY with encouraging results has catapulted into the market novel nutraceutical or health supplements for therapeutic or prophylactic intervention based on the consumption of mono-specific or mixed IgY formulations. With recent trends in consumer preference for natural materials to alleviate health concerns, the increasing healthcare costs and the recent advances in drug delivery systems, IgY is likely to shift from its mainly functional food status toward pharmaceuticalization in the foreseeable future.


Asunto(s)
Enfermedades Transmisibles/terapia , Enfermedades del Sistema Digestivo/prevención & control , Enfermedades del Sistema Digestivo/terapia , Inmunización Pasiva/métodos , Inmunoglobulinas/administración & dosificación , Factores Inmunológicos/administración & dosificación , Administración Oral , Animales , Ensayos Clínicos como Asunto , Evaluación Preclínica de Medicamentos , Humanos , Inmunoglobulinas/inmunología , Factores Inmunológicos/inmunología
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