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SARS-CoV-2 infection in hospital areas is of a particular concern, since the close interaction between health care personnel and patients diagnosed with COVID-19, which allows virus to be easily spread between them and subsequently to their families and communities. Preventing SARS-CoV-2 infection among healthcare personnel is essential to reduce the frequency of infections and outbreaks during the pandemic considering that they work in high-risk areas. In this research, silver nanoparticles (AgNPs) were tested in vitro and shown to have an inhibitory effect on SARS-CoV-2 infection in cultured cells. Subsequently, we assess the effects of mouthwash and nose rinse with ARGOVIT® silver nanoparticles (AgNPs), in the prevention of SARS-CoV-2 contagion in health workers consider as high-risk group of acquiring the infection in the General Tijuana Hospital, Mexico, a hospital for the exclusive recruitment of patients diagnosed with COVID-19. We present a prospective randomized study of 231 participants that was carried out for 9 weeks (during the declaration of a pandemic). The “experimental” group was instructed to do mouthwash and nose rinse with the AgNPs solution; the “control” group was instructed to do mouthwashes and nose rinse in a conventional way. The incidence of SARS-CoV-2 infection was significantly lower in the “experimental” group (two participants of 114, 1.8%) compared to the “control” group (thirty-three participants of 117, 28.2%), with a 84.8% efficiency. We conclude that the mouth and nasal rinse with AgNPs helps in the prevention of SARS-CoV-2 infection in health personnel who are exposed to patients diagnosed with COVID-19.
Horacio Almanza-Reyes; Sandra Moreno; Ismael Plascencia-López; Martha Alvarado-Vera; Leslie Patrón-Romero; Belén Borrego; Alberto Reyes-Escamilla; Daniel Valencia-Manzo; Alejandro Brun; Alexey Pestryakov; Nina Bogdanchikova. Evaluation of silver nanoparticles for the prevention of SARS-CoV-2 infection in health workers: in vitro and in vivo. 2021, 1 .
AMA StyleHoracio Almanza-Reyes, Sandra Moreno, Ismael Plascencia-López, Martha Alvarado-Vera, Leslie Patrón-Romero, Belén Borrego, Alberto Reyes-Escamilla, Daniel Valencia-Manzo, Alejandro Brun, Alexey Pestryakov, Nina Bogdanchikova. Evaluation of silver nanoparticles for the prevention of SARS-CoV-2 infection in health workers: in vitro and in vivo. . 2021; ():1.
Chicago/Turabian StyleHoracio Almanza-Reyes; Sandra Moreno; Ismael Plascencia-López; Martha Alvarado-Vera; Leslie Patrón-Romero; Belén Borrego; Alberto Reyes-Escamilla; Daniel Valencia-Manzo; Alejandro Brun; Alexey Pestryakov; Nina Bogdanchikova. 2021. "Evaluation of silver nanoparticles for the prevention of SARS-CoV-2 infection in health workers: in vitro and in vivo." , no. : 1.
Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus that causes an important disease in ruminants, with great economic losses. The infection can be also transmitted to humans; therefore, it is considered a major threat to both human and animal health. In a previous work, we described a novel RVFV variant selected in cell culture in the presence of the antiviral agent favipiravir that was highly attenuated in vivo. This variant displayed 24 amino acid substitutions in different viral proteins when compared to its parental viral strain, two of them located in the NSs protein that is known to be the major virulence factor of RVFV. By means of a reverse genetics system, in this work we have analyzed the effect that one of these substitutions, P82L, has in viral attenuation in vivo. Rescued viruses carrying this single amino acid change were clearly attenuated in BALB/c mice while their growth in an interferon (IFN)-competent cell line as well as the production of interferon beta (IFN-β) did not seem to be affected. However, the pattern of nuclear NSs accumulation was modified in cells infected with the mutant viruses. These results highlight the key role of the NSs protein in the modulation of viral infectivity.
Belén Borrego; Sandra Moreno; Nuria de la Losa; Friedemann Weber; Alejandro Brun. The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice. Viruses 2021, 13, 542 .
AMA StyleBelén Borrego, Sandra Moreno, Nuria de la Losa, Friedemann Weber, Alejandro Brun. The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice. Viruses. 2021; 13 (4):542.
Chicago/Turabian StyleBelén Borrego; Sandra Moreno; Nuria de la Losa; Friedemann Weber; Alejandro Brun. 2021. "The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice." Viruses 13, no. 4: 542.
Rift valley fever virus (RVFV) is a mosquito-borne bunyavirus that causes an important disease in ruminants, with great economic losses. The infection can be also transmitted to humans; therefore it is considered a major threat to both human and animal health. In a previous work, we described a novel RVFV variant selected in cell culture in the presence of the antiviral agent favipiravir that was highly attenuated in vivo. This variant displayed 24 amino acid substitutions in different viral proteins when compared to its parental viral strain, two of them located in the NSs protein that is known to be the major virulence factor of RVFV. By means of a reverse genetics system, in this work we have analyzed the effect that one of these substitutions, P82L, has in viral attenuation in vivo. Rescued viruses carrying this single amino acid change were clearly attenuated in BALB/c mice while their growth in an IFN-competent cell line as well as the production of IFN-β did not seem to be affected. However, the pattern of nuclear NSs accumulation was modified in cells infected with the mutant viruses. These results unveil a new RVFV virulence marker highlighting the multiple ways of NSs protein to modulate viral infectivity.
Belén Borrego; Sandra Moreno; Nuria de la Losa; Friedemann Weber; Alejandro Brun. The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice Not Related with a Type-I IFN Antagonistic Phenotype. 2021, 1 .
AMA StyleBelén Borrego, Sandra Moreno, Nuria de la Losa, Friedemann Weber, Alejandro Brun. The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice Not Related with a Type-I IFN Antagonistic Phenotype. . 2021; ():1.
Chicago/Turabian StyleBelén Borrego; Sandra Moreno; Nuria de la Losa; Friedemann Weber; Alejandro Brun. 2021. "The Change P82L in the Rift Valley Fever Virus NSs Protein Confers Attenuation in Mice Not Related with a Type-I IFN Antagonistic Phenotype." , no. : 1.
SUMMARY/ABSTRACTIn a previous work, we showed that favipiravir, a promising drug with antiviral activity against a number of RNA viruses, led to the extinction of RVFV from infected cell cultures. Nevertheless, certain drug concentrations allowed the recovery of a virus variant showing increased resistance to favipiravir. In this work, we characterized this novel resistant variant both at genomic and phenotypic level in vitro and in vivo. Interestingly, the resistant virus displayed reduced growth rates in insect cells and was highly attenuated but still immunogenic in vivo. Some amino acid substitutions were identified in the viral RNA-dependent RNA-polymerase (RdRp) gene and in the encoded IFN antagonist NSs gene, in catalytic core motifs and nuclear localization associated positions respectively. These data may help to characterize novel potential virulence markers, offering additional strategies for further safety improvements of RVF live attenuated vaccine candidates.SIGNIFICANCE STATEMENTLive attenuated virus vaccines usually provide long lasting immune responses upon administration. These vaccines are not recommended for use in immune compromised hosts, due to the presence of uncontrolled residual virulence. Cell culture virus propagation in the presence of mutagenic drugs often results in weakened virus lacking virulence as well as limited spreading capabilities. Here, we have characterized a mutagen-induced RVFV variant (40F-p8) that is not virulent in a highly sensitive mouse strain lacking antiviral response. The observed lack of virulence correlates with the presence of specific mutations along key residues in the viral genome, unveiling potential virulence determinants. Thus, 40F-p8 constitutes the basis for a novel RVFV vaccine strain with additional safety features.
Belén Borrego; Alejandro Brun. A hyper-attenuated variant of Rift Valley fever virus (RVFV) generated by a mutagenic drug (favipiravir) unveils potential virulence markers. 2020, 1 .
AMA StyleBelén Borrego, Alejandro Brun. A hyper-attenuated variant of Rift Valley fever virus (RVFV) generated by a mutagenic drug (favipiravir) unveils potential virulence markers. . 2020; ():1.
Chicago/Turabian StyleBelén Borrego; Alejandro Brun. 2020. "A hyper-attenuated variant of Rift Valley fever virus (RVFV) generated by a mutagenic drug (favipiravir) unveils potential virulence markers." , no. : 1.
We report the generation, characterization and epitope mapping of a panel of 26 monoclonal antibodies (MAbs) against the VP1 capsid protein of feline calicivirus (FCV). Two close but distinct linear epitopes were identified at the capsid outermost surface (P2 subdomain) of VP1, within the E5′HVR antigenic hypervariable region: one spanning amino acids 431-435 (PAGDY), highly conserved and recognized by non-neutralizing MAbs; and a second epitope spanning amino acids 445-451 (ITTANQY), highly variable and recognized by neutralizing MAbs. These antibodies might be valuable for diagnostic applications, as well as for further research in different aspects of the biology of FCV.
Carolina Cubillos-Zapata; Iván Angulo; Horacio Almanza; Belén Borrego; María Zamora-Ceballos; José R. Castón; Ignacio Mena; Esther Blanco; Juan Bárcena. Precise location of linear epitopes on the capsid surface of feline calicivirus recognized by neutralizing and non-neutralizing monoclonal antibodies. Veterinary Research 2020, 51, 1 -8.
AMA StyleCarolina Cubillos-Zapata, Iván Angulo, Horacio Almanza, Belén Borrego, María Zamora-Ceballos, José R. Castón, Ignacio Mena, Esther Blanco, Juan Bárcena. Precise location of linear epitopes on the capsid surface of feline calicivirus recognized by neutralizing and non-neutralizing monoclonal antibodies. Veterinary Research. 2020; 51 (1):1-8.
Chicago/Turabian StyleCarolina Cubillos-Zapata; Iván Angulo; Horacio Almanza; Belén Borrego; María Zamora-Ceballos; José R. Castón; Ignacio Mena; Esther Blanco; Juan Bárcena. 2020. "Precise location of linear epitopes on the capsid surface of feline calicivirus recognized by neutralizing and non-neutralizing monoclonal antibodies." Veterinary Research 51, no. 1: 1-8.
In vitro neutralizing antibodies have been often correlated with protection against Rift Valley fever virus (RVFV) infection. We have reported previously that a single inoculation of sucrose-purified modified vaccinia Ankara (MVA) encoding RVFV glycoproteins (rMVAGnGc) was sufficient to induce a protective immune response in mice after a lethal RVFV challenge. Protection was related to the presence of glycoprotein specific CD8+ cells, with a low-level detection of in vitro neutralizing antibodies. In this work we extended those observations aimed to explore the role of humoral responses after MVA vaccination and to study the contribution of each glycoprotein antigen to the protective efficacy. Thus, we tested the efficacy and immune responses in BALB/c mice of recombinant MVA viruses expressing either glycoprotein Gn (rMVAGn) or Gc (rMVAGc). In the absence of serum neutralizing antibodies, our data strongly suggest that protection of vaccinated mice upon the RVFV challenge can be achieved by the activation of cellular responses mainly directed against Gc epitopes. The involvement of cellular immunity was stressed by the fact that protection of mice was strain dependent. Furthermore, our data suggest that the rMVA based single dose vaccination elicits suboptimal humoral immune responses against Gn antigen since disease in mice was exacerbated upon virus challenge in the presence of rMVAGnGc or rMVAGn immune serum. Thus, Gc-specific cellular immunity could be an important component in the protection after the challenge observed in BALB/c mice, contributing to the elimination of infected cells reducing morbidity and mortality and counteracting the deleterious effect of a subneutralizing antibody immune response.
Elena López-Gil; Sandra Moreno; Javier Ortego; Belén Borrego; Gema Lorenzo; Alejandro Brun. MVA Vectored Vaccines Encoding Rift Valley Fever Virus Glycoproteins Protect Mice against Lethal Challenge in the Absence of Neutralizing Antibody Responses. Vaccines 2020, 8, 82 .
AMA StyleElena López-Gil, Sandra Moreno, Javier Ortego, Belén Borrego, Gema Lorenzo, Alejandro Brun. MVA Vectored Vaccines Encoding Rift Valley Fever Virus Glycoproteins Protect Mice against Lethal Challenge in the Absence of Neutralizing Antibody Responses. Vaccines. 2020; 8 (1):82.
Chicago/Turabian StyleElena López-Gil; Sandra Moreno; Javier Ortego; Belén Borrego; Gema Lorenzo; Alejandro Brun. 2020. "MVA Vectored Vaccines Encoding Rift Valley Fever Virus Glycoproteins Protect Mice against Lethal Challenge in the Absence of Neutralizing Antibody Responses." Vaccines 8, no. 1: 82.
Foot‐and‐mouth disease virus (FMDV) causes a widely extended contagious disease of livestock. We have previously reported that a synthetic dendrimeric peptide, termed B2T(mal), consisting of two copies of a B‐cell epitope [VP1(140‐158)] linked through maleimide groups to a T‐cell epitope [3A(21‐35)] of FMDV, elicits potent B‐ and T‐cell specific responses and confers solid protection in pigs to type O FMDV challenge. Longer duration of the protective response as well as the possibility of inducing protection after a single dose are important requirements for an efficient FMD vaccine. Herein, we show that administration of two doses of B2T(mal) elicited high levels of specific total IgGs and neutralizing antibodies that lasted 4‐5 months after the peptide boost. Additionally, concomitant levels of IFN‐γ producing specific T‐cells were observed. Immunization with two doses of B2T(mal) conferred a long‐lasting reduced susceptibility to FMDV infection, up to 136 days (19/20 weeks) post‐boost. Remarkably, a similar duration of the protective response was achieved by a single dose of B2T(mal). The effect on the B2T(mal) vaccine of RNA transcripts derived from non‐coding regions in the FMDV genome, known to enhance the immune response and protection induced by a conventional inactivated vaccine, was also analyzed. The contribution of our results to the development of FMD dendrimeric vaccines is discussed.
Rodrigo Cañas‐Arranz; Mar Forner; Sira Defaus; Miguel Rodríguez‐Pulido; Patricia De León; Elisa Torres; María J. Bustos; Belén Borrego; Margarita Sáiz; Esther Blanco; David Andreu; Francisco Sobrino. A bivalent B‐cell epitope dendrimer peptide can confer long‐lasting immunity in swine against foot‐and‐mouth disease. Transboundary and Emerging Diseases 2020, 67, 1614 -1622.
AMA StyleRodrigo Cañas‐Arranz, Mar Forner, Sira Defaus, Miguel Rodríguez‐Pulido, Patricia De León, Elisa Torres, María J. Bustos, Belén Borrego, Margarita Sáiz, Esther Blanco, David Andreu, Francisco Sobrino. A bivalent B‐cell epitope dendrimer peptide can confer long‐lasting immunity in swine against foot‐and‐mouth disease. Transboundary and Emerging Diseases. 2020; 67 (4):1614-1622.
Chicago/Turabian StyleRodrigo Cañas‐Arranz; Mar Forner; Sira Defaus; Miguel Rodríguez‐Pulido; Patricia De León; Elisa Torres; María J. Bustos; Belén Borrego; Margarita Sáiz; Esther Blanco; David Andreu; Francisco Sobrino. 2020. "A bivalent B‐cell epitope dendrimer peptide can confer long‐lasting immunity in swine against foot‐and‐mouth disease." Transboundary and Emerging Diseases 67, no. 4: 1614-1622.
Currently, silver nanoparticles (AgNPs) are extensively studied for biomedical applications, but although nanomaterials provide many benefits, recently their comparative toxicity have barely been explored. In the current work, AgNPs toxicity on biological systems of different levels of complexity was assessed in a comprehensive and comparatively way. The organisms included viruses, bacteria, microalgae, fungi, animal and human cells (including cancer cell lines). We found that growth of biological systems of different taxonomical groups –in vitro, at a cellular level- is inhibited at concentrations of AgNPs within the same order of magnitude (101 μg/ml). Thus, the AgNPs toxicity does not depend on the complexity of the organisms. The fact that cells and virus are inhibited with a concentration of AgNPs within the same order of magnitude could be explained considering that silver affects fundamental structures for cells and virus alike.
Roberto Vázquez-Muñoz; Belén Borrego-Rivero; Karla Oyuky Juárez-Moreno; Maritza Roxana García-García; Josué David Mota-Morales; Nina Bogdanchikova; Alejandro Huerta-Saquero. Silver Nanoparticles as Nanoantibiotics: A Comparative Analysis of their Toxicity on Biological Systems of Different Complexity. Revista de Ciencias Tecnológicas 2018, 1, 8 -11.
AMA StyleRoberto Vázquez-Muñoz, Belén Borrego-Rivero, Karla Oyuky Juárez-Moreno, Maritza Roxana García-García, Josué David Mota-Morales, Nina Bogdanchikova, Alejandro Huerta-Saquero. Silver Nanoparticles as Nanoantibiotics: A Comparative Analysis of their Toxicity on Biological Systems of Different Complexity. Revista de Ciencias Tecnológicas. 2018; 1 (1):8-11.
Chicago/Turabian StyleRoberto Vázquez-Muñoz; Belén Borrego-Rivero; Karla Oyuky Juárez-Moreno; Maritza Roxana García-García; Josué David Mota-Morales; Nina Bogdanchikova; Alejandro Huerta-Saquero. 2018. "Silver Nanoparticles as Nanoantibiotics: A Comparative Analysis of their Toxicity on Biological Systems of Different Complexity." Revista de Ciencias Tecnológicas 1, no. 1: 8-11.
Currently, nanomaterials are more frequently in our daily life, specifically in biomedicine, electronics, food, textiles and catalysis just to name a few. Although nanomaterials provide many benefits, recently their toxicity profiles have begun to be explored. In this work, the toxic effects of silver nanoparticles (35nm-average diameter and Polyvinyl-Pyrrolidone-coated) on biological systems of different levels of complexity was assessed in a comprehensive and comparatively way, through a variety of viability and toxicological assays. The studied organisms included viruses, bacteria, microalgae, fungi, animal and human cells (including cancer cell lines). It was found that biological systems of different taxonomical groups are inhibited at concentrations of silver nanoparticles within the same order of magnitude. Thus, the toxicity of nanomaterials on biological/living systems, constrained by their complexity, e.g. taxonomic groups, resulted contrary to the expected. The fact that cells and virus are inhibited with a concentration of silver nanoparticles within the same order of magnitude could be explained considering that silver nanoparticles affects very primitive cellular mechanisms by interacting with fundamental structures for cells and virus alike.
Roberto Vazquez-Munoz; Belen Borrego; Karla Oyuky Juarez-Moreno; Maritza García-García; Josue Mota-Morales; Nina Bogdanchikova; Alejandro Huerta-Saquero. Toxicity of silver nanoparticles in biological systems: Does the complexity of biological systems matter? Toxicology Letters 2017, 276, 11 -20.
AMA StyleRoberto Vazquez-Munoz, Belen Borrego, Karla Oyuky Juarez-Moreno, Maritza García-García, Josue Mota-Morales, Nina Bogdanchikova, Alejandro Huerta-Saquero. Toxicity of silver nanoparticles in biological systems: Does the complexity of biological systems matter? Toxicology Letters. 2017; 276 ():11-20.
Chicago/Turabian StyleRoberto Vazquez-Munoz; Belen Borrego; Karla Oyuky Juarez-Moreno; Maritza García-García; Josue Mota-Morales; Nina Bogdanchikova; Alejandro Huerta-Saquero. 2017. "Toxicity of silver nanoparticles in biological systems: Does the complexity of biological systems matter?" Toxicology Letters 276, no. : 11-20.
Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious disease and a major concern in animal health worldwide. We have previously reported the use of RNA transcripts mimicking structural domains in the non-coding regions of the FMDV RNA as potent type-I interferon (IFN) inducers showing antiviral effect in vivo, as well as their immunomodulatory properties in combination with an FMD vaccine in mice. Here, we describe the enhancing effect of RNA delivery on the immunogenicity and protection induced by a suboptimal dose of a conventional FMD vaccine in pigs. Animals receiving the RNA developed earlier and higher levels of neutralizing antibodies against homologous and heterologous isolates, compared to those immunized with the vaccine alone, and had higher anti-FMDV titers at late times post-vaccination. RNA delivery also induced higher specific T-cell response and protection levels against FMDV challenge. Peripheral blood mononuclear cells from pigs inoculated with RNA and the vaccine had a higher IFN-γ specific response than those from pigs receiving the vaccine alone. When challenged with FMDV, all three animals immunized with the conventional vaccine developed antibodies to the non-structural viral proteins 3ABC and two of them developed severe signs of disease. In the group receiving the vaccine together with the RNA, two pigs were fully protected while one showed delayed and mild signs of disease. Our results support the immunomodulatory effect of these RNA molecules in natural hosts and suggest their potential use for improvement of FMD vaccines strategies.
Belén Borrego; Esther Blanco; Miguel Rodríguez Pulido; Francisco Mateos; Gema Lorenzo; Sabrina Cardillo; Eliana Smitsaart; Francisco Sobrino; Margarita Sáiz. Combined administration of synthetic RNA and a conventional vaccine improves immune responses and protection against foot-and-mouth disease virus in swine. Antiviral Research 2017, 142, 30 -36.
AMA StyleBelén Borrego, Esther Blanco, Miguel Rodríguez Pulido, Francisco Mateos, Gema Lorenzo, Sabrina Cardillo, Eliana Smitsaart, Francisco Sobrino, Margarita Sáiz. Combined administration of synthetic RNA and a conventional vaccine improves immune responses and protection against foot-and-mouth disease virus in swine. Antiviral Research. 2017; 142 ():30-36.
Chicago/Turabian StyleBelén Borrego; Esther Blanco; Miguel Rodríguez Pulido; Francisco Mateos; Gema Lorenzo; Sabrina Cardillo; Eliana Smitsaart; Francisco Sobrino; Margarita Sáiz. 2017. "Combined administration of synthetic RNA and a conventional vaccine improves immune responses and protection against foot-and-mouth disease virus in swine." Antiviral Research 142, no. : 30-36.
In this work we have tested the potential antiviral activity of silver nanoparticles formulated as Argovit™ against Rift Valley fever virus (RVFV). The antiviral activity of Argovit was tested on Vero cell cultures and in type-I interferon receptor deficient mice (IFNAR −/− mice) by two different approaches: (i) different dilutions of Argovit were added to previously infected cells or administrated to animals infected with a lethal dose of virus; (ii) virus was pre-incubated with different dilutions of Argovit before inoculation in mice or cells. Though the ability of silver nanoparticles to control an ongoing RVFV infection in the conditions tested was limited, the incubation of virus with Argovit before the infection led to a reduction of the infectivity titers both in vitro and in vivo. These results reveal the potential application of silver nanoparticles to control the infectivity of RVFV, which is an important zoonotic pathogen.
Belén Borrego; Gema Lorenzo; Josué D. Mota-Morales; Horacio Almanza-Reyes; Francisco Mateos; Elena López-Gil; Nuria de la Losa; Vasily A. Burmistrov; Alexey Pestryakov; Alejandro Brun; Nina Bogdanchikova. Potential application of silver nanoparticles to control the infectivity of Rift Valley fever virus in vitro and in vivo. Nanomedicine: Nanotechnology, Biology and Medicine 2016, 12, 1185 -1192.
AMA StyleBelén Borrego, Gema Lorenzo, Josué D. Mota-Morales, Horacio Almanza-Reyes, Francisco Mateos, Elena López-Gil, Nuria de la Losa, Vasily A. Burmistrov, Alexey Pestryakov, Alejandro Brun, Nina Bogdanchikova. Potential application of silver nanoparticles to control the infectivity of Rift Valley fever virus in vitro and in vivo. Nanomedicine: Nanotechnology, Biology and Medicine. 2016; 12 (5):1185-1192.
Chicago/Turabian StyleBelén Borrego; Gema Lorenzo; Josué D. Mota-Morales; Horacio Almanza-Reyes; Francisco Mateos; Elena López-Gil; Nuria de la Losa; Vasily A. Burmistrov; Alexey Pestryakov; Alejandro Brun; Nina Bogdanchikova. 2016. "Potential application of silver nanoparticles to control the infectivity of Rift Valley fever virus in vitro and in vivo." Nanomedicine: Nanotechnology, Biology and Medicine 12, no. 5: 1185-1192.
The innate immune system is the first line of defense against viral infections. Exploiting innate responses for antiviral, therapeutic and vaccine adjuvation strategies is being extensively explored. We have previously described, the ability of small in vitro RNA transcripts, mimicking the sequence and structure of different domains in the non-coding regions of the foot-and-mouth disease virus (FMDV) genome (ncRNAs), to trigger a potent and rapid innate immune response. These synthetic non-infectious molecules have proved to have a broad-range antiviral activity and to enhance the immunogenicity of an FMD inactivated vaccine in mice. Here, we have studied the involvement of pattern-recognition receptors (PRRs) in the ncRNA-induced innate response and analyzed the antiviral and cytokine profiles elicited in swine cultured cells, as well as peripheral blood mononuclear cells (PBMCs).
Belén Borrego; Miguel Rodríguez-Pulido; Concepción Revilla; Belén Álvarez; Francisco Sobrino; Javier Domínguez; Margarita Sáiz. Synthetic RNAs Mimicking Structural Domains in the Foot-and-Mouth Disease Virus Genome Elicit a Broad Innate Immune Response in Porcine Cells Triggered by RIG-I and TLR Activation. Viruses 2015, 7, 3954 -3973.
AMA StyleBelén Borrego, Miguel Rodríguez-Pulido, Concepción Revilla, Belén Álvarez, Francisco Sobrino, Javier Domínguez, Margarita Sáiz. Synthetic RNAs Mimicking Structural Domains in the Foot-and-Mouth Disease Virus Genome Elicit a Broad Innate Immune Response in Porcine Cells Triggered by RIG-I and TLR Activation. Viruses. 2015; 7 (7):3954-3973.
Chicago/Turabian StyleBelén Borrego; Miguel Rodríguez-Pulido; Concepción Revilla; Belén Álvarez; Francisco Sobrino; Javier Domínguez; Margarita Sáiz. 2015. "Synthetic RNAs Mimicking Structural Domains in the Foot-and-Mouth Disease Virus Genome Elicit a Broad Innate Immune Response in Porcine Cells Triggered by RIG-I and TLR Activation." Viruses 7, no. 7: 3954-3973.
In this work we have addressed the effect of synthetic, non-infectious, RNA transcripts, mimicking structural domains of the non-coding regions (NCRs) of the foot-and-mouth disease virus (FMDV) genome on the infection of mice with Rift Valley fever virus (RVFV). Groups of 5 mice were inoculated intraperitoneally (i.p.) with 200 μg of synthetic RNA resembling the 5′-terminal S region, the internal ribosome entry site (IRES) or the 3′-NCR of the FMDV genome. RNA inoculation was performed 24 h before (−24 h), 24 h after (+24 h) or simultaneously to the challenge with a lethal dose of RVFV. Administration of the IRES RNA afforded higher survival rates than administration of S or 3′NCR transcripts either at −24 h or +24 h after challenge. In contrast, when RNA inoculation and viral challenge were performed simultaneously, all mice survived in both IRES- and 3′NCR-inoculated groups, with an 80% survival in mice receiving the S RNA. Among survivors, a complete correlation between significant anti-RVFV circulating antibody titers and resistance to a second lethal challenge with the virus was observed, supporting a limited viral replication in the RNA-inoculated animals upon the first challenge. All three RNA transcripts were able to induce the production of systemic antiviral and pro-inflammatory cytokines. These data show that triggering of intracellular pathogen sensing pathways constitutes a promising approach towards development of novel RVF preventive or therapeutic strategies.
Gema Lorenzo; Miguel Rodríguez-Pulido; Elena López-Gil; Francisco Sobrino; Belén Borrego; Margarita Sáiz; Alejandro Brun. Protection against Rift Valley fever virus infection in mice upon administration of interferon-inducing RNA transcripts from the FMDV genome. Antiviral Research 2014, 109, 64 -67.
AMA StyleGema Lorenzo, Miguel Rodríguez-Pulido, Elena López-Gil, Francisco Sobrino, Belén Borrego, Margarita Sáiz, Alejandro Brun. Protection against Rift Valley fever virus infection in mice upon administration of interferon-inducing RNA transcripts from the FMDV genome. Antiviral Research. 2014; 109 ():64-67.
Chicago/Turabian StyleGema Lorenzo; Miguel Rodríguez-Pulido; Elena López-Gil; Francisco Sobrino; Belén Borrego; Margarita Sáiz; Alejandro Brun. 2014. "Protection against Rift Valley fever virus infection in mice upon administration of interferon-inducing RNA transcripts from the FMDV genome." Antiviral Research 109, no. : 64-67.
Belén Borrego; Miguel Rodríguez-Pulido; Francisco Mateos; Nuria De La Losa; Francisco Sobrino; Margarita Sáiz. Delivery of synthetic RNA can enhance the immunogenicity of vaccines against foot-and-mouth disease virus (FMDV) in mice. Vaccine 2013, 31, 4375 -4381.
AMA StyleBelén Borrego, Miguel Rodríguez-Pulido, Francisco Mateos, Nuria De La Losa, Francisco Sobrino, Margarita Sáiz. Delivery of synthetic RNA can enhance the immunogenicity of vaccines against foot-and-mouth disease virus (FMDV) in mice. Vaccine. 2013; 31 (40):4375-4381.
Chicago/Turabian StyleBelén Borrego; Miguel Rodríguez-Pulido; Francisco Mateos; Nuria De La Losa; Francisco Sobrino; Margarita Sáiz. 2013. "Delivery of synthetic RNA can enhance the immunogenicity of vaccines against foot-and-mouth disease virus (FMDV) in mice." Vaccine 31, no. 40: 4375-4381.
Development of efficient and safer vaccines against foot-and-mouth disease virus (FMDV) is a must. Previous results obtained in our laboratory have demonstrated that DNA vaccines encoding B and T cell epitopes from type C FMDV, efficiently controlled virus replication in mice, while they did not protect against FMDV challenge in pigs, one of the FMDV natural hosts. The main finding of this work is the ability to improve the protection afforded in swine using a new DNA-vaccine prototype (pCMV-APCH1BTT), encoding FMDV B and T-cell epitopes fused to the single-chain variable fragment of the 1F12 mouse monoclonal antibody that recognizes Class-II Swine Leukocyte antigens. Half of the DNA-immunized pigs were fully protected upon viral challenge, while the remaining animals were partially protected, showing a delayed, shorter and milder disease than control pigs. Full protection in a given vaccinated-pig correlated with the induction of specific IFNγ-secreting T-cells, detectable prior to FMDV-challenge, together with a rapid development of neutralizing antibodies after viral challenge, pointing towards the relevance that both arms of the immune response can play in protection. Our results open new avenues for developing future FMDV subunit vaccines.
Belén Borrego; Jordi M. Argilaguet; Eva Perez-Martin; Javier Domínguez; Mariano Pérez-Filgueira; Jose M. Escribano; Francisco Sobrino; Fernando Rodríguez. A DNA vaccine encoding foot-and-mouth disease virus B and T-cell epitopes targeted to class II swine leukocyte antigens protects pigs against viral challenge. Antiviral Research 2011, 92, 359 -363.
AMA StyleBelén Borrego, Jordi M. Argilaguet, Eva Perez-Martin, Javier Domínguez, Mariano Pérez-Filgueira, Jose M. Escribano, Francisco Sobrino, Fernando Rodríguez. A DNA vaccine encoding foot-and-mouth disease virus B and T-cell epitopes targeted to class II swine leukocyte antigens protects pigs against viral challenge. Antiviral Research. 2011; 92 (2):359-363.
Chicago/Turabian StyleBelén Borrego; Jordi M. Argilaguet; Eva Perez-Martin; Javier Domínguez; Mariano Pérez-Filgueira; Jose M. Escribano; Francisco Sobrino; Fernando Rodríguez. 2011. "A DNA vaccine encoding foot-and-mouth disease virus B and T-cell epitopes targeted to class II swine leukocyte antigens protects pigs against viral challenge." Antiviral Research 92, no. 2: 359-363.
Despite several attempts to design new vaccines, there are as of yet no available alternatives to the conventional FMDV vaccines. Here, we present the divergent results obtained in pigs after immunization with two experimental DNA vaccines encoding one B and two T cell FMDV epitopes, either expressed alone (pCMV-BTT) or fused to a strong signal peptide (pCMV-spBTT). While all pigs vaccinated with pCMV-spBTT showed both a delay in the disease onset and reduced severity of signs and lesions after FMDV challenge, pigs immunized with pCMV-BTT showed an exacerbation of the disease and most of the pigs remained viremic at 10 days post-infection, the end-point of the experiment, thus opening concerns about FMDV-suboptimal immunization. Interestingly, only one of the four pigs vaccinated with pCMV-spBTT showed neutralizing antibodies before challenge, demonstrating that partial protection against FMDV could be afforded in the absence of preexisting neutralizing antibodies.
Llilianne Ganges; Belén Borrego; Paloma Fernández-Pacheco; Concepción Revilla; Natalia Fernández-Borges; Javier Domínguez; Francisco Sobrino; Fernando Rodríguez. DNA immunization of pigs with foot-and-mouth disease virus minigenes: From partial protection to disease exacerbation. Virus Research 2011, 157, 121 -125.
AMA StyleLlilianne Ganges, Belén Borrego, Paloma Fernández-Pacheco, Concepción Revilla, Natalia Fernández-Borges, Javier Domínguez, Francisco Sobrino, Fernando Rodríguez. DNA immunization of pigs with foot-and-mouth disease virus minigenes: From partial protection to disease exacerbation. Virus Research. 2011; 157 (1):121-125.
Chicago/Turabian StyleLlilianne Ganges; Belén Borrego; Paloma Fernández-Pacheco; Concepción Revilla; Natalia Fernández-Borges; Javier Domínguez; Francisco Sobrino; Fernando Rodríguez. 2011. "DNA immunization of pigs with foot-and-mouth disease virus minigenes: From partial protection to disease exacerbation." Virus Research 157, no. 1: 121-125.
In previous work we have reported the immunization of swine using in vitro-transcribed foot-and-mouth disease virus (FMDV) RNA. With the aim of testing whether RNA-induced immunization can mediate protection against viral infection, a group of Swiss adult mice was inoculated with FMDV infectious transcripts. In most inoculated animals viral RNA was detected in serum at 48-72 h postinoculation. A group of the RNA-inoculated mice (11 out of 19) developed significant titers of neutralizing antibodies against FMDV. Among those animals that were successfully challenged with infectious virus (15 out of 19), three out of the eight animals immunized upon RNA inoculation were protected, as infectious virus could not be isolated from sera but specific anti-FMDV antibodies could be readily detected. These results suggest the potential of the inoculation of genetically engineered FMDV RNA for virulence and protection assays in the murine model and allow to explore the suitability of RNA-based FMDV vaccination in natural host animals.
Miguel Rodríguez Pulido; Francisco Sobrino; Belén Borrego; Margarita Sáiz. RNA immunization can protect mice against foot-and-mouth disease virus. Antiviral Research 2010, 85, 556 -558.
AMA StyleMiguel Rodríguez Pulido, Francisco Sobrino, Belén Borrego, Margarita Sáiz. RNA immunization can protect mice against foot-and-mouth disease virus. Antiviral Research. 2010; 85 (3):556-558.
Chicago/Turabian StyleMiguel Rodríguez Pulido; Francisco Sobrino; Belén Borrego; Margarita Sáiz. 2010. "RNA immunization can protect mice against foot-and-mouth disease virus." Antiviral Research 85, no. 3: 556-558.
Outbreaks of foot and mouth disease virus (FMDV) have devastating economic consequences in affected areas. The presence of multiple serotypes and virus variants makes vaccination complicated. A better understanding of protective immune mechanisms may help in development of novel vaccines with cross protective capacity. While much attention has been devoted to humoral responses to FMDV, less is known about the role of cell-mediated responses in protective immunity. Predictions of potential CTL epitopes by two different computer algorithms identified the viral 2C protein as containing a potential murine H2-Kd CTL epitope located in its amino-terminal half. DNA vaccination of mice with a plasmid expressing the 2C protein and a fragment thereof confirmed that this was indeed a CTL epitope, as shown by interferon gamma (IFN-γ) induction in CD8+, CD44hi splenocytes after in vitro stimulation with peptides containing the amino acid sequence KYKDAKEWL, predicted for the CTL epitope. A peptide with the variant sequence KYKEAKEWL induced similar responses, indicating tolerability towards a conservative substitution at the altered residue. Virus infection likewise induced a measurable CTL response against KYKDAKEWL, although less clear due to a higher background of IFN-γ production in splenocytes from infected mice. Challenge of vaccinated mice showed that the CTL response induced by the 2C protein was not protective, since viremia and mortality were unaffected by vaccination. The implications for vaccine development are discussed in the context of cross-serotype reactive responses.
Annette Malene Barfoed; Fernando Rodriguez; Dominic Therrien; Belen Borrego; Francisco Sobrino; Søren Kamstrup. DNA immunization with 2C FMDV non-structural protein reveals the presence of an immunodominant CD8+, CTL epitope for Balb/c mice. Antiviral Research 2006, 72, 178 -189.
AMA StyleAnnette Malene Barfoed, Fernando Rodriguez, Dominic Therrien, Belen Borrego, Francisco Sobrino, Søren Kamstrup. DNA immunization with 2C FMDV non-structural protein reveals the presence of an immunodominant CD8+, CTL epitope for Balb/c mice. Antiviral Research. 2006; 72 (3):178-189.
Chicago/Turabian StyleAnnette Malene Barfoed; Fernando Rodriguez; Dominic Therrien; Belen Borrego; Francisco Sobrino; Søren Kamstrup. 2006. "DNA immunization with 2C FMDV non-structural protein reveals the presence of an immunodominant CD8+, CTL epitope for Balb/c mice." Antiviral Research 72, no. 3: 178-189.