RESUMEN
Certain strains of fowl adenovirus serotype 4 (FAdV-4) of the family Adenoviridae are recognized to be the causative agents of Hydropericardium Syndrome (HPS) in broiler chicken. Despite the significantly spiking mortality in broilers due to HPS, not much effort has been made to design an effective vaccine against FAdV-4. The combination of immuno- and bioinformatics tools for immunogenic epitope prediction is the most recent concept of vaccine design. It reduces the time and effort required for hunting a potent vaccine candidate and is economical. Previously, we have reported the penton base protein of FAdV-4 to be a candidate for subunit vaccine against HPS. In the present study, we have computationally pre-screened promising B- and T-cell epitopes of the penton base. Multiple methods were employed for linear B-cell epitope identification; BepiPred and five other methods based on physicochemical properties of the amino acids. The penton base was homology modeled by means of Modeller 9.17 and after refinement of the model (by GalaxyRefine web server) ElliPro web tool was used to predict the discontinuous epitopes. NetMHCcons 1.1 and NetMHCIIpan 3.1 servers were used for the likelihood of peptide binding to Major Histocompatibility Complex (MHC) class I & II molecules respectively for T-cell epitope forecast. As a result, we identified the peptide stretch of 1-225⯠as the most promiscuous B- and T-cell epitope region in penton base Full Length (FL) protein sequence. Escherichia coli based expression vectors were generated containing cloned peptide stretch 1-225 (penton base1-225) and penton base FL gene sequence. The recombinant penton base1-225 and penton base FL proteins were expressed and purified using Escherichia coli-based expression system. Purification yield of penton base1-225 was 3-fold higher compared to penton base FL. These proteins were injected in chickens to determine their competence in protection against HPS. The results showed equal protection level of the two proteins and the commercial inactivated vaccine against FAdV-4 infection. The results suggest the peptide stretch 1-225 of penton base as a valuable candidate for developing an epitope-driven vaccine to combat HPS.
Asunto(s)
Infecciones por Adenoviridae/veterinaria , Vacunas contra el Adenovirus/inmunología , Aviadenovirus/inmunología , Proteínas de la Cápside/inmunología , Epítopos/inmunología , Pericardio/patología , Enfermedades de las Aves de Corral/virología , Infecciones por Adenoviridae/inmunología , Infecciones por Adenoviridae/prevención & control , Vacunas contra el Adenovirus/administración & dosificación , Vacunas contra el Adenovirus/genética , Animales , Aviadenovirus/genética , Proteínas de la Cápside/genética , Pollos/inmunología , Simulación por Computador , Mapeo Epitopo/métodos , Epítopos/genética , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito T/inmunología , Modelos Moleculares , Pericardio/virología , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/prevención & control , Serogrupo , Síndrome , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunologíaRESUMEN
Novel immunological tools for efficient diagnosis and treatment of emerging infections are urgently required. Advances in the diagnostic and vaccine development fields are continuously progressing, with reverse vaccinology and structural vaccinology (SV) methods for antigen identification and structure-based antigen (re)design playing increasingly relevant roles. SV, in particular, is predicted to be the front-runner in the future development of diagnostics and vaccines targeting challenging diseases such as AIDS and cancer. We review state-of-the-art methodologies for structure-based epitope identification and antigen design, with specific applicative examples. We highlight the implications of such methods for the engineering of biomolecules with improved immunological properties, potential diagnostic and/or therapeutic uses, and discuss the perspectives of structure-based rational design for the production of advanced immunoreagents.
Asunto(s)
Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/terapia , Vacunas/uso terapéutico , Virosis/diagnóstico , Virosis/terapia , Antígenos/química , Infecciones Bacterianas/inmunología , Portadores de Fármacos/uso terapéutico , Epítopos/química , Humanos , Nanopartículas/química , Pruebas Serológicas/métodos , Vacunas/inmunología , Virosis/inmunologíaRESUMEN
Is the US ready for a biological attack using Ebola virus or Anthrax? Will vaccine developers be able to produce a Zika virus vaccine, before the epidemic spreads around the world? A recent report by The Blue Ribbon Study Panel on Biodefense argues that the US is not ready for these challenges, however, technologies and capabilities that could address these deficiencies are within reach. Vaccine technologies have advanced and readiness has improved in recent years, due to advances in sequencing technology and computational power making the 'vaccines on demand' concept a reality. Building a robust strategy to design effective biodefense vaccines from genome sequences harvested by real-time biosurveillance will benefit from technologies that are being brought to bear on the cancer cure 'moonshot'. When combined with flexible vaccine production platforms, vaccines on demand will relegate expensive and, in some cases, insufficiently effective vaccine stockpiles to the dust heap of history.
Asunto(s)
Investigación Biomédica/métodos , Defensa Civil/métodos , Tecnología Farmacéutica/métodos , Vacunas/inmunología , Vacunas/aislamiento & purificación , Animales , Investigación Biomédica/tendencias , Defensa Civil/tendencias , Humanos , Tecnología Farmacéutica/tendencias , Estados UnidosRESUMEN
Computational vaccine design, also known as computational vaccinology, encompasses epitope mapping, antigen selection and immunogen design using computational tools. The iVAX toolkit is an integrated set of tools that has been in development since 1998 by De Groot and Martin. It comprises a suite of immunoinformatics algorithms for triaging candidate antigens, selecting immunogenic and conserved T cell epitopes, eliminating regulatory T cell epitopes, and optimizing antigens for immunogenicity and protection against disease. iVAX has been applied to vaccine development programs for emerging infectious diseases, cancer antigens and biodefense targets. Several iVAX vaccine design projects have had success in pre-clinical studies in animal models and are progressing toward clinical studies. The toolkit now incorporates a range of immunoinformatics tools for infectious disease and cancer immunotherapy vaccine design. This article will provide a guide to the iVAX approach to computational vaccinology.