RESUMEN
Since late 2010, outbreaks of porcine epidemic diarrhea (PED) have been reported in the swine industry in China. A variant PEDV strain that differs from strain CV777 causes prevalent PEDV infections which commercial vaccines based on CV777 cannot provide complete protection. In this study, we designed a new vaccine based on the epidemic PEDV strain AH2012/12, adjuvanted with flagellin, a mucosal adjuvant that induces mucosal and systemic production of IgA. Three groups of pregnant sows were immunized twice, with a 14-day interval, with PEDV adjuvanted with flagellin, PEDV alone, or PBS before farrowing, and newborn piglets from each group were selected and challenged with PEDV. Immunization with this vaccine elicited high levels of IgG, IgA, and neutralizing antibodies in the serum and colostrum of sows, and newborn piglets were protected against PEDV while suckling. This study should guide the prevention and control strategies for PEDV infection, thereby reducing the losses associated with this virus.
Asunto(s)
Infecciones por Coronavirus/veterinaria , Flagelina/administración & dosificación , Virus de la Diarrea Epidémica Porcina/inmunología , Enfermedades de los Porcinos/prevención & control , Vacunas Virales/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Animales , Animales Recién Nacidos , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Línea Celular , Calostro/química , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/prevención & control , Femenino , Flagelina/inmunología , Inmunización , Embarazo , Porcinos , Enfermedades de los Porcinos/patología , Vacunas de Productos Inactivados/inmunología , Vacunas Virales/administración & dosificaciónAsunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/terapia , Flagelina/inmunología , Flagelina/uso terapéutico , Inmunidad Innata/inmunología , Neutrófilos/inmunología , Neumonía Viral/inmunología , Neumonía Viral/terapia , Receptor Toll-Like 5/inmunología , Animales , Antivirales/farmacología , Antivirales/uso terapéutico , Proteínas Reguladoras de la Apoptosis/metabolismo , Betacoronavirus/inmunología , COVID-19 , Proteínas de Unión al Calcio/metabolismo , Quimioterapia Adyuvante , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/prevención & control , Desoxirribonucleasa I/metabolismo , Desoxirribonucleasa I/farmacología , Desoxirribonucleasa I/uso terapéutico , Flagelina/administración & dosificación , Humanos , Inmunidad Innata/efectos de los fármacos , Inflamación/complicaciones , Inflamación/inmunología , Inflamación/patología , Virus de la Influenza A/inmunología , Interferón beta/biosíntesis , Interferón beta/inmunología , Interleucina-18/inmunología , Ratones , Modelos Inmunológicos , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Pandemias/prevención & control , Péptidos/uso terapéutico , Neumonía Viral/complicaciones , Neumonía Viral/prevención & control , Pseudomonas aeruginosa/inmunología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/inmunología , SARS-CoV-2 , Receptor Toll-Like 5/agonistasRESUMEN
For subunit vaccines, adjuvants play a key role in shaping the magnitude, persistence and form of targeted antigen-specific immune response. Flagellin is a potent immune activator by bridging innate inflammatory responses and adaptive immunity and an adjuvant candidate for clinical application. Calcium phosphate nanoparticles are efficient carriers for different biomolecules like DNA, RNA, peptides and proteins. Flagellin-functionalized calcium phosphate nanoparticles were prepared and their immunostimulatory effect on the innate immune system, i.e. the cytokine production, was studied. They induced the production of the proinflammatory cytokines IL-8 (Caco-2 cells) and IL-1ß (bone marrow-derived macrophages; BMDM) in vitro and IL-6 in vivo after intraperitoneal injection in mice. The immunostimulation was more pronounced than with free flagellin.
Asunto(s)
Vacunas Bacterianas/inmunología , Fosfatos de Calcio/administración & dosificación , Portadores de Fármacos/administración & dosificación , Flagelina/inmunología , Inmunidad Innata , Nanopartículas/administración & dosificación , Animales , Vacunas Bacterianas/administración & dosificación , Células CACO-2 , Femenino , Flagelina/administración & dosificación , Humanos , Inyecciones Intraperitoneales , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Ratones , Ratones Endogámicos C57BL , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/inmunologíaRESUMEN
Mistletoe extract (ME) is applied as an adjuvant treatment in cancer therapy in thousands of patients each year in Europe. The main immunostimulating component of mistletoe extract, mistletoe lectin, recently has been shown to be a pattern recognition receptor ligand and hence is binding to an important class of pathogen-sensing receptors. Pattern recognition receptor ligands are potent activators of dendritic cells. This activation is a prerequisite for a full-blown T-cell response against cancer cells. Pattern recognition receptor ligands are increasingly recognized as important players in cancer immunotherapy. We collect evidence from case studies on spontaneous regression, from epidemiology, from experiments in a mouse cancer model, and from protein structure comparisons to argue that a combination of mistletoe therapy with other pattern recognition receptor ligand substances leads to an increased immune stimulatory effect. We show that mistletoe lectin is a plant protein of bacterial origin with a 3D structure very similar to shiga toxin from Shigella dysenteriae, which explains the remarkable immunogenicity of mistletoe lectin. Secondly, we show that a combination of pattern recognition receptor ligands applied metronomically in a cancer mouse model leads to complete remission, while single pattern recognition receptor ligands slowed tumor growth. Taken together, we propose to combine mistletoe drugs with other pattern recognition receptor ligand drugs to increase its efficacy in adjuvant or even primary cancer therapy.