Co-inoculation of baculovirus and FMDV vaccine in mice, elicits very early protection against foot and mouth disease virus without interfering with long lasting immunity

Quattrocchi, Valeria; Molinari, Paula; Langellotti, Cecilia; Gnazzo, Victoria; Taboga, Oscar; Zamorano, Patricia

doi:10.1016/j.vaccine.2013.03.067

Cited by 22 publications

(15 citation statements)

References 28 publications

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“…Additionally, because IFN-␣ and IFN-␥ are recognized to be vaccine adjuvants, it can be expected that use of the combination treatment evaluated in this study with an FMD vaccine would facilitate improved immune responses and antibody formation (40)(41)(42). Use of a combination of IFN inducers and the FMDV vaccine has been reported previously, and enhanced inhibition of FMDV was observed in those studies (43,44). In future studies, we propose to use a combination of Adporcine IFN-␣␥ and Ad-3siRNA with a vaccine to evaluate their combined effects.…”

Section: Discussionsupporting

confidence: 53%

Robust Protection against Highly Virulent Foot-and-Mouth Disease Virus in Swine by Combination Treatment with Recombinant Adenoviruses Expressing Porcine Alpha and Gamma Interferons and Multiple Small Interfering RNAs

Kim

Park

Lee

et al. 2015

J Virol

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Because the currently available vaccines against foot-and-mouth disease (FMD) provide no protection until 4 to 7 days postvaccination, the only alternative method to halt the spread of the FMD virus (FMDV) during outbreaks is the application of antiviral agents. Combination treatment strategies have been used to enhance the efficacy of antiviral agents, and such strategies may be advantageous in overcoming viral mechanisms of resistance to antiviral treatments. We have developed recombinant adenoviruses (Ads) for the simultaneous expression of porcine alpha and gamma interferons (Ad-porcine IFN-␣␥) as well as 3 small interfering RNAs (Ad-3siRNA) targeting FMDV mRNAs encoding nonstructural proteins. The antiviral effects of Ad-porcine IFN-␣␥ and Ad-3siRNA expression were tested in combination in porcine cells, suckling mice, and swine. We observed enhanced antiviral effects in porcine cells and mice as well as robust protection against the highly pathogenic strain O/Andong/ SKR/2010 and increased expression of cytokines in swine following combination treatment. In addition, we showed that combination treatment was effective against all serotypes of FMDV. Therefore, we suggest that the combined treatment with Adporcine IFN-␣␥ and Ad-3siRNA may offer fast-acting antiviral protection and be used with a vaccine during the period that the vaccine does not provide protection against FMD. IMPORTANCEThe use of current foot-and-mouth disease (FMD) vaccines to induce rapid protection provides limited effectiveness because the protection does not become effective until a minimum of 4 days after vaccination. Therefore, during outbreaks antiviral agents remain the only available treatment to confer rapid protection and reduce the spread of foot-and-mouth disease virus (FMDV) in livestock until vaccine-induced protective immunity can become effective. Interferons (IFNs) and small interfering RNAs (siRNAs) have been reported to be effective antiviral agents against FMDV, although the virus has associated mechanisms of resistance to type I interferons and siRNAs. We have developed recombinant adenoviruses for the simultaneous expression of porcine alpha and gamma interferons (Ad-porcine IFN-␣␥) as well as 3 small interfering RNAs (Ad-3siRNA) to enhance the inhibitory effects of these antiviral agents observed in previous studies. Here, we show enhanced antiviral effects against FMDV by combination treatment with Ad-porcine IFN-␣␥ and Ad-3siRNA to overcome the mechanisms of resistance of FMDV in swine.

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Section: Discussionsupporting

confidence: 53%

Robust Protection against Highly Virulent Foot-and-Mouth Disease Virus in Swine by Combination Treatment with Recombinant Adenoviruses Expressing Porcine Alpha and Gamma Interferons and Multiple Small Interfering RNAs

Kim

Park

Lee

et al. 2015

J Virol

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“…Protection against FMDV was assessed, as described previously [17]. In brief, mice were inoculated i.p.…”

Section: Viral Challengementioning

confidence: 99%

“…It has been demonstrated that a proinflammatory response characterized by IL-6 and IFN-g secretion is associated with the early protection observed in iFMDV-vaccinated mice [17]. To investigate if Gal-8 was inducing this inflammatory response, the presence of IL-6 and IFN-g was analyzed in the supernatants of splenocyte cultures from mice at 2, 5, and 21 dpi.…”

Section: Gal-8 Enhances the Elicitation Of The Immune Response Againsmentioning

confidence: 99%

Galectin-8 activates dendritic cells and stimulates antigen-specific immune response elicitation

Carabelli

Quattrocchi²,

D'antuono

et al. 2017

Journal of Leukocyte Biology

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Galectin-8 (Gal-8) is a mammalian β-galactoside-binding lectin, endowed with proinflammatory properties. Given its capacity to enhance antigen-specific immune responses in vivo, we investigated whether Gal-8 was also able to promote APC activation to sustain T cell activation after priming. Both endogenous [dendritic cells (DCs)] and bone marrow-derived DCs (BMDCs) treated with exogenous Gal-8 exhibited a mature phenotype characterized by increased MHC class II (MHCII), CD80, and CD86 surface expression. Moreover, Gal-8-treated BMDCs (Gal-8-BMDCs) stimulated antigen-specific T cells more efficiently than immature BMDCs (iBMDCs). Proinflammatory cytokines IL-3, IL-2, IL-6, TNF, MCP-1, and MCP-5, as well as growth factor G-CSF, were augmented in Gal-8-BMDC conditioned media, with IL-6 as the most prominent. Remarkably, BMDCs from Gal-8-deficient mice ( BMDC) displayed reduced CD86 and IL-6 expression and an impaired ability to promote antigen-specific CD4 T cell activation. To test if Gal-8-induced activation correlates with the elicitation of an effective immune response, soluble Gal-8 was coadministrated with antigen during immunization of BALB/cJ mice in the experimental foot-and-mouth disease virus (FMDV) model. When a single dose of Gal-8 was added to the antigen formulation, an increased specific and neutralizing humoral response was developed, sufficient to enhance animal protection upon viral challenge. IL-6 and IFN-γ, as well as lymphoproliferative responses, were also incremented in Gal-8/antigen-immunized animals only at 48 h after immunization, suggesting that Gal-8 induces the elicitation of an inflammatory response at an early stage. Taking together, these findings argue in favor of the use of Gal-8 as an immune-stimulator molecule to enhance the adaptive immune response.

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“…Por otro lado, mediante ingeniería genética se han desarrollado diferentes estrategias de presentación de antígenos heterólogos que permiten por un lado la expresión del antígeno dentro de la célula de mamífero o la generación de baculovirus quiméricos para diferentes proteínas estructurales, obteniendo así viriones que transportan las proteínas de interés como proteínas estructurales del virión brotado. Estos atributos han propiciado su uso no sólo como adyuvante de la vacuna [83]- [86], sino también como vector vacunal en sí mismo.…”

Section: Tabla Ii: Vacunas Aprobadas Producidas En El Sistema Bv Paraunclassified

“…Este modelo imita en parte el curso de la infección de FMDV en el hospedador natural, permitiendo evaluar varios aspectos de la patogenicidad. Diversos gmpos de investigación, incluido el nuestro, han utilizado ampliamente este modelo [45], [86], [161].…”

Section: Experimentos De Desafío Con A/arg/2001 En El Modelo Ratónunclassified

Diseño racional de una vacuna recombinante contra el virus de la fiebre aftosa vectorizada e inmunomodulada por baculovirus

Tavarone¹

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El presente proyecto tiene como objetivo diseñar de manera racional un candidato vacunal recombinante contra la fiebre aftosa basado en vectores báculo virales. Tiene como hipótesis que la localización de antígenos en diferentes posiciones de la partícula viral, en combinación con las propiedades antivirales, de presentación multimérica, de inmunomodulación y facilidad de producción biotecnológica del baculovirus ^cMNPV, redundarán en un efecto sinérgico, brindando sólidas respuestas inmunes humorales y celulares. Tiene como finalidad contribuir al control de enfermedades de interés veterinario empleando estrategias combinadas de presentación antigénica y antivirales. Para el diseño racional, en primer lugar definiremos las implicancias de la localización del antígeno en la partícula viral y la estrategia de presentación, así como el efecto de la formulación de los baculovirus recombinantes con diferentes adyuvantes de uso veterinario aprobado en los diferentes tipos de respuesta. Los resultados obtenidos empleando un antígeno modelo serán luego aplicados al diseño y evaluación de un BV recombinante que transporte antígenos específicos como candidato vacunal para FMDV-A/Arg/2001.

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Co-inoculation of baculovirus and FMDV vaccine in mice, elicits very early protection against foot and mouth disease virus without interfering with long lasting immunity

Cited by 22 publications

References 28 publications

Robust Protection against Highly Virulent Foot-and-Mouth Disease Virus in Swine by Combination Treatment with Recombinant Adenoviruses Expressing Porcine Alpha and Gamma Interferons and Multiple Small Interfering RNAs

Robust Protection against Highly Virulent Foot-and-Mouth Disease Virus in Swine by Combination Treatment with Recombinant Adenoviruses Expressing Porcine Alpha and Gamma Interferons and Multiple Small Interfering RNAs

Galectin-8 activates dendritic cells and stimulates antigen-specific immune response elicitation

Diseño racional de una vacuna recombinante contra el virus de la fiebre aftosa vectorizada e inmunomodulada por baculovirus

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