The Experts below are selected from a list of 201 Experts worldwide ranked by ideXlab platform
Erna Geessien Kroon - One of the best experts on this subject based on the ideXlab platform.
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Multi-walled carbon nanotubes functionalized with recombinant Dengue Virus 3 envelope proteins induce significant and specific immune responses in mice.
Journal of nanobiotechnology, 2017Co-Authors: Alice F. Versiani, Erna Geessien Kroon, Ruiz G. Astigarraga, Ana Paula M. Barboza, Milene A. Rachid, Daniele G. Souza, Luiz O. Ladeira, Edel F. Barbosa-stancioli, Eliseu Soares De Oliveira Rocha, Ado JorioAbstract:Dengue is the most prevalent arthropod-borne viral disease in the world. In this article we present results on the development, characterization and immunogenic evaluation of an alternative vaccine candidate against Dengue. The MWNT-DENV3E nanoconjugate was developed by covalent functionalization of carboxylated multi-walled carbon nanotubes (MWNT) with recombinant Dengue envelope (DENV3E) proteins. The recombinant antigens were bound to the MWNT using a diimide-activated amidation process and the immunogen was characterized by TEM, AFM and Raman Spectroscopy. Furthermore, the immunogenicity of this vaccine candidate was evaluated in a murine model. Immunization with MWNT-DENV3E induced comparable IgG responses in relation to the immunization with non-conjugated proteins; however, the inoculation of the nanoconjugate into mice generated higher titers of neutralizing antibodies. Cell-mediated responses were also evaluated, and higher Dengue-specific splenocyte proliferation was observed in cell cultures derived from mice immunized with MWNT-DENV3E when compared to animals immunized with the non-conjugated DENV3E. Despite the recent licensure of the CYD-TDV Dengue vaccine in some countries, results from the vaccine’s phase III trial have cast doubts about its overall efficacy and global applicability. While questions about the effectiveness of the CYD-TDV vaccine still lingers, it is wise to keep at hand an array of vaccine candidates, including alternative non-classical approaches like the one presented here.
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Infection of the central nervous system with Dengue Virus 3 genotype I causing neurological manifestations in Brazil
Revista da Sociedade Brasileira de Medicina Tropical, 2016Co-Authors: Danilo Bretas De Oliveira, Guilherme Machado, Gabriel Magno De Freitas Almeida, Paulo César Peregrino Ferreira, Cláudio A. Bonjardim, Giliane De Souza Trindade, Jônatas Santos Abrahão, Erna Geessien KroonAbstract:A case of Dengue Virus 3 (DENV-3) genotype I infection with neurological manifestations occurred in Belo Horizonte, Minas Gerais in October 2012. The serotype was detected by PCR, and the genotype was assessed by sequencing and phylogenetic analysis of the C-prM region. The Virus causing neurological manifestations clustered with other sequences of DENV-3 genotype I. Because neurological manifestations of DENV are possibly misdiagnosed in Brazil, this study serves as an alert of the importance of DENV diagnoses in CNS infections.
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Dengue Virus 3 genotype i in aedes aegypti mosquitoes and eggs brazil 2005 2006
Emerging Infectious Diseases, 2010Co-Authors: Ana Paula Pessoa Vilela, Paulo César Peregrino Ferreira, Cláudio A. Bonjardim, Leandra Barcelos Figueiredo, João Rodrigues Dos Santos, Alvaro E. Eiras, Erna Geessien KroonAbstract:Dengue Virus type 3 genotype I was detected in Brazil during epidemics in 2002–2004. To confirm this finding, we identified this Virus genotype in naturally infected field-caught Aedes aegypti mosquitoes and eggs. Results showed usefulness of Virus investigations in vectors as a component of active epidemiologic surveillance.
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Dengue Virus 3 clinical isolates show different patterns of virulence in experimental mice infection.
Microbes and infection, 2010Co-Authors: Gustavo Portela Ferreira, Paulo César Peregrino Ferreira, Cláudio A. Bonjardim, Leandra Barcelos Figueiredo, Luiz Felipe Leomil Coelho, Policarpo Ademar Sales Junior, Alzira Batista Cecílio, Rosa Maria Esteves Arantes, Marco Antônio Campos, Erna Geessien KroonAbstract:Dengue Virus (DENV) may cause symptomatic infection with mild, undifferentiated febrile illness called classical Dengue fever (DF) or a more severe disease, potentially fatal, known as Dengue hemorrhagic fever (DHF) or Dengue shock syndrome. The pathogenesis of DHF is based on the virulence of the infecting DENV and depends on the infecting serotypes and genotypes; it is also based on the immunopathogenesis that is mediated by host immune responses, including Dengue Virus-cross-reactive antibodies that augment the severity of infections. Involvement of central nervous system (CNS) is extensively described. The present study describes the virulence of DENV-3 isolates in a mouse model by intracranial (i.c.) inoculation with genotypes I and III. Our data suggest that, in this experimental model, DENV-3 genotype I may have the propensity to cause neurological disease in mice, whereas the genotype III is associated with asymptomatic infection in mice. Additionally, the symptomatic mice show a decrease of white blood cell count, infectious DENV in the brains and alterations in levels of IFN-gamma, IL-6 and MCP-1. The results confirm the mouse model as a way to study the biology of DENV-3 isolates and to improve the knowledge about the neurovirulence of the different genotypes of DENV.
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Dengue Virus 3 Genotype I in Aedes aegypti Mosquitoes and Eggs, Brazil, 2005–2006
Emerging infectious diseases, 2010Co-Authors: Ana Paula Pessoa Vilela, Paulo César Peregrino Ferreira, Cláudio A. Bonjardim, Leandra Barcelos Figueiredo, João Rodrigues Dos Santos, Alvaro E. Eiras, Erna Geessien KroonAbstract:Dengue Virus type 3 genotype I was detected in Brazil during epidemics in 2002–2004. To confirm this finding, we identified this Virus genotype in naturally infected field-caught Aedes aegypti mosquitoes and eggs. Results showed usefulness of Virus investigations in vectors as a component of active epidemiologic surveillance.
Angel Balmaseda - One of the best experts on this subject based on the ideXlab platform.
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Analysis of Individuals from a Dengue-Endemic Region Helps Define the Footprint and Repertoire of Antibodies Targeting Dengue Virus 3 Type-Specific Epitopes.
mBio, 2017Co-Authors: Daniela V. Andrade, Angel Balmaseda, Leah C. Katzelnick, Douglas G. Widman, Aravinda M. De Silva, Ralph S. Baric, Eva HarrisAbstract:The four Dengue Virus serotypes (DENV1 to 4) cause Dengue, a major public health problem worldwide. Individuals exposed to primary DENV infections develop serotype-specific neutralizing antibodies, including strongly neutralizing antibodies targeting quaternary epitopes. To date, no studies have measured the levels and kinetics of serum antibodies directed to such epitopes among populations in regions where Dengue is endemic. Here, we use a recombinant DENV4 (rDENV4/3-M14) displaying a major DENV3 type-specific quaternary epitope recognized by human monoclonal antibody 5J7 to measure the proportion, magnitude, and kinetics of DENV3 type-specific neutralizing antibody responses targeting this epitope. Primary DENV3 sera from 30 individuals in a Dengue hospital-based study in Nicaragua were studied 3, 6, 12, and 18 months post-infection, alongside samples collected annually 1 to 4 years post-primary DENV3 infection from 10 individuals in a cohort study in Nicaragua. We found substantial individual variation in the proportion of DENV3 type-specific neutralizing antibody titers attributed to the 5J7 epitope (range, 0 to 100%), with the mean significantly increasing from 22.6% to 41.4% from 3 to 18 months. We extended the transplanted DENV3 5J7 epitope on the virion (rDENV4/3-M16), resulting in increased recognition in several individuals, helping define the footprint of the epitope. However, 37% and 13% of the subjects still showed little to no recognition of the 5J7 epitope at 3 and 18 months, respectively, indicating that one or more additional DENV3 type-specific epitopes exist. Overall, this study demonstrates how DENV-immune plasma from populations from areas of endemicity, when coupled with structurally guided recombinant Viruses, can help characterize the epitope-specific neutralizing antibody response in natural DENV infections, with direct implications for design and evaluation of Dengue vaccines.IMPORTANCE The four serotypes of Dengue Virus cause Dengue, a major public health burden worldwide, yet it has been challenging to develop a vaccine that is safe and equally effective against all four serotypes. More in-depth characterization of natural human neutralizing antibody responses is needed to identify determinants of protective antibody responses to all DENV serotypes. Here, we use hospital and cohort studies in a region where Dengue is endemic to assess the proportion and kinetics of the DENV3 neutralizing antibody response directed to a quaternary epitope on DENV3 recognized by strongly neutralizing human monoclonal antibody 5J7, which was transplanted into a DENV4 backbone. We show that many individuals recognized the 5J7 epitope, but to various degrees over time, suggesting that additional DENV3-specific epitopes likely exist. Thus, characterization of epitope-specific neutralizing antibody responses in natural DENV infections can help define the footprint and repertoire of antibodies directed to DENV3 type-specific epitopes, with implications for Dengue vaccine development.
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Correlation between Dengue-Specific Neutralizing Antibodies and Serum Avidity in Primary and Secondary Dengue Virus 3 Natural Infections in Humans
PLoS neglected tropical diseases, 2013Co-Authors: Andreas S. Puschnik, Angel Balmaseda, Louis Lau, Elizabeth A. Cromwell, Simona Zompi, Eva HarrisAbstract:Although heterotypic secondary infection with Dengue Virus (DENV) is associated with severe disease, the majority of secondary infections are mild or asymptomatic. The mechanisms of antibody-mediated protection are poorly understood. In 2010, 108 DENV3-positive cases were enrolled in a pediatric hospital-based study in Managua, Nicaragua, with 61 primary and 47 secondary infections. We analyzed DENV-specific neutralization titers (NT50), IgM and IgG avidity, and antibody titer in serum samples collected during acute and convalescent phases and 3, 6, and 18 months post-infection. NT50 titers peaked at convalescence and decreased thereafter. IgG avidity to DENV3 significantly increased between convalescent and 3-month time-points in primary DENV infections and between the acute and convalescent phase in secondary DENV infections. While avidity to DENV2, a likely previous infecting serotype, was initially higher than avidity to DENV3 in secondary DENV infections, the opposite relation was observed 3-18 months post-infection. We found significant correlations between IgM avidity and NT50 in acute primary cases and between IgG avidity and NT50 in secondary DENV infections. In summary, our findings indicate that IgM antibodies likely play a role in early control of DENV infections. IgG serum avidity to DENV, analyzed for the first time in longitudinal samples, switches from targeting mainly cross-reactive serotype(s) to the current infecting serotype over time. Finally, serum avidity correlates with neutralization capacity.
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Unusual Dengue Virus 3 epidemic in Nicaragua, 2009.
PLoS neglected tropical diseases, 2011Co-Authors: Gamaliel Gutierrez, Katherine Standish, Federico Narvaez, Maria Angeles Perez, Saira Saborio, Douglas Elizondo, Oscar Ortega, Andrea Nuñez, Guillermina Kuan, Angel BalmasedaAbstract:The four Dengue Virus serotypes (DENV1–4) cause the most prevalent mosquito-borne viral disease affecting humans worldwide. In 2009, Nicaragua experienced the largest Dengue epidemic in over a decade, marked by unusual clinical presentation, as observed in two prospective studies of pediatric Dengue in Managua. From August 2009–January 2010, 212 Dengue cases were confirmed among 396 study participants at the National Pediatric Reference Hospital. In our parallel community-based cohort study, 170 Dengue cases were recorded in 2009–10, compared to 13–65 cases in 2004–9. In both studies, significantly more patients experienced “compensated shock” (poor capillary refill plus cold extremities, tachycardia, tachypnea, and/or weak pulse) in 2009–10 than in previous years (42.5% [90/212] vs. 24.7% [82/332] in the hospital study (p
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unusual Dengue Virus 3 epidemic in nicaragua 2009
PLOS Neglected Tropical Diseases, 2011Co-Authors: Gamaliel Gutierrez, Katherine Standish, Federico Narvaez, Maria Angeles Perez, Saira Saborio, Douglas Elizondo, Oscar Ortega, Andrea Nuñez, Guillermina Kuan, Angel BalmasedaAbstract:The four Dengue Virus serotypes (DENV1–4) cause the most prevalent mosquito-borne viral disease affecting humans worldwide. In 2009, Nicaragua experienced the largest Dengue epidemic in over a decade, marked by unusual clinical presentation, as observed in two prospective studies of pediatric Dengue in Managua. From August 2009–January 2010, 212 Dengue cases were confirmed among 396 study participants at the National Pediatric Reference Hospital. In our parallel community-based cohort study, 170 Dengue cases were recorded in 2009–10, compared to 13–65 cases in 2004–9. In both studies, significantly more patients experienced “compensated shock” (poor capillary refill plus cold extremities, tachycardia, tachypnea, and/or weak pulse) in 2009–10 than in previous years (42.5% [90/212] vs. 24.7% [82/332] in the hospital study (p<0.001) and 17% [29/170] vs. 2.2% [4/181] in the cohort study (p<0.001). Signs of poor peripheral perfusion presented significantly earlier (1–2 days) in 2009–10 than in previous years according to Kaplan-Meier survival analysis. In the hospital study, 19.8% of subjects were transferred to intensive care, compared to 7.1% in previous years – similar to the cohort study. DENV-3 predominated in 2008–9, 2009–10, and 2010–11, and full-length sequencing revealed no major genetic changes from 2008–9 to 2010–11. In 2008–9 and 2010–11, typical Dengue was observed; only in 2009–10 was unusual presentation noted. Multivariate analysis revealed only “2009–10” as a significant risk factor for Dengue Fever with Compensated Shock. Interestingly, circulation of pandemic influenza A-H1N1 2009 in Managua was shifted such that it overlapped with the Dengue epidemic. We hypothesize that prior influenza A H1N1 2009 infection may have modulated subsequent DENV infection, and initial results of an ongoing study suggest increased risk of shock among children with anti-H1N1-2009 antibodies. This study demonstrates that parameters other than serotype, viral genomic sequence, immune status, and sequence of serotypes can play a role in modulating Dengue disease outcome.
Ado Jorio - One of the best experts on this subject based on the ideXlab platform.
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Multi-walled carbon nanotubes functionalized with recombinant Dengue Virus 3 envelope proteins induce significant and specific immune responses in mice
Journal of Nanobiotechnology, 2017Co-Authors: Alice F. Versiani, Ruiz G. Astigarraga, Eliseu S. O. Rocha, Ana Paula M. Barboza, Erna G. Kroon, Milene A. Rachid, Daniele G. Souza, Luiz O. Ladeira, Edel F. Barbosa-stancioli, Ado JorioAbstract:Background Dengue is the most prevalent arthropod-borne viral disease in the world. In this article we present results on the development, characterization and immunogenic evaluation of an alternative vaccine candidate against Dengue. Methods The MWNT-DENV3E nanoconjugate was developed by covalent functionalization of carboxylated multi-walled carbon nanotubes (MWNT) with recombinant Dengue envelope (DENV3E) proteins. The recombinant antigens were bound to the MWNT using a diimide-activated amidation process and the immunogen was characterized by TEM, AFM and Raman Spectroscopy. Furthermore, the immunogenicity of this vaccine candidate was evaluated in a murine model. Results Immunization with MWNT-DENV3E induced comparable IgG responses in relation to the immunization with non-conjugated proteins; however, the inoculation of the nanoconjugate into mice generated higher titers of neutralizing antibodies. Cell-mediated responses were also evaluated, and higher Dengue-specific splenocyte proliferation was observed in cell cultures derived from mice immunized with MWNT-DENV3E when compared to animals immunized with the non-conjugated DENV3E. Conclusions Despite the recent licensure of the CYD-TDV Dengue vaccine in some countries, results from the vaccine’s phase III trial have cast doubts about its overall efficacy and global applicability. While questions about the effectiveness of the CYD-TDV vaccine still lingers, it is wise to keep at hand an array of vaccine candidates, including alternative non-classical approaches like the one presented here.
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Multi-walled carbon nanotubes functionalized with recombinant Dengue Virus 3 envelope proteins induce significant and specific immune responses in mice.
Journal of nanobiotechnology, 2017Co-Authors: Alice F. Versiani, Erna Geessien Kroon, Ruiz G. Astigarraga, Ana Paula M. Barboza, Milene A. Rachid, Daniele G. Souza, Luiz O. Ladeira, Edel F. Barbosa-stancioli, Eliseu Soares De Oliveira Rocha, Ado JorioAbstract:Dengue is the most prevalent arthropod-borne viral disease in the world. In this article we present results on the development, characterization and immunogenic evaluation of an alternative vaccine candidate against Dengue. The MWNT-DENV3E nanoconjugate was developed by covalent functionalization of carboxylated multi-walled carbon nanotubes (MWNT) with recombinant Dengue envelope (DENV3E) proteins. The recombinant antigens were bound to the MWNT using a diimide-activated amidation process and the immunogen was characterized by TEM, AFM and Raman Spectroscopy. Furthermore, the immunogenicity of this vaccine candidate was evaluated in a murine model. Immunization with MWNT-DENV3E induced comparable IgG responses in relation to the immunization with non-conjugated proteins; however, the inoculation of the nanoconjugate into mice generated higher titers of neutralizing antibodies. Cell-mediated responses were also evaluated, and higher Dengue-specific splenocyte proliferation was observed in cell cultures derived from mice immunized with MWNT-DENV3E when compared to animals immunized with the non-conjugated DENV3E. Despite the recent licensure of the CYD-TDV Dengue vaccine in some countries, results from the vaccine’s phase III trial have cast doubts about its overall efficacy and global applicability. While questions about the effectiveness of the CYD-TDV vaccine still lingers, it is wise to keep at hand an array of vaccine candidates, including alternative non-classical approaches like the one presented here.
Alice F. Versiani - One of the best experts on this subject based on the ideXlab platform.
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Multi-walled carbon nanotubes functionalized with recombinant Dengue Virus 3 envelope proteins induce significant and specific immune responses in mice
Journal of Nanobiotechnology, 2017Co-Authors: Alice F. Versiani, Ruiz G. Astigarraga, Eliseu S. O. Rocha, Ana Paula M. Barboza, Erna G. Kroon, Milene A. Rachid, Daniele G. Souza, Luiz O. Ladeira, Edel F. Barbosa-stancioli, Ado JorioAbstract:Background Dengue is the most prevalent arthropod-borne viral disease in the world. In this article we present results on the development, characterization and immunogenic evaluation of an alternative vaccine candidate against Dengue. Methods The MWNT-DENV3E nanoconjugate was developed by covalent functionalization of carboxylated multi-walled carbon nanotubes (MWNT) with recombinant Dengue envelope (DENV3E) proteins. The recombinant antigens were bound to the MWNT using a diimide-activated amidation process and the immunogen was characterized by TEM, AFM and Raman Spectroscopy. Furthermore, the immunogenicity of this vaccine candidate was evaluated in a murine model. Results Immunization with MWNT-DENV3E induced comparable IgG responses in relation to the immunization with non-conjugated proteins; however, the inoculation of the nanoconjugate into mice generated higher titers of neutralizing antibodies. Cell-mediated responses were also evaluated, and higher Dengue-specific splenocyte proliferation was observed in cell cultures derived from mice immunized with MWNT-DENV3E when compared to animals immunized with the non-conjugated DENV3E. Conclusions Despite the recent licensure of the CYD-TDV Dengue vaccine in some countries, results from the vaccine’s phase III trial have cast doubts about its overall efficacy and global applicability. While questions about the effectiveness of the CYD-TDV vaccine still lingers, it is wise to keep at hand an array of vaccine candidates, including alternative non-classical approaches like the one presented here.
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Multi-walled carbon nanotubes functionalized with recombinant Dengue Virus 3 envelope proteins induce significant and specific immune responses in mice.
Journal of nanobiotechnology, 2017Co-Authors: Alice F. Versiani, Erna Geessien Kroon, Ruiz G. Astigarraga, Ana Paula M. Barboza, Milene A. Rachid, Daniele G. Souza, Luiz O. Ladeira, Edel F. Barbosa-stancioli, Eliseu Soares De Oliveira Rocha, Ado JorioAbstract:Dengue is the most prevalent arthropod-borne viral disease in the world. In this article we present results on the development, characterization and immunogenic evaluation of an alternative vaccine candidate against Dengue. The MWNT-DENV3E nanoconjugate was developed by covalent functionalization of carboxylated multi-walled carbon nanotubes (MWNT) with recombinant Dengue envelope (DENV3E) proteins. The recombinant antigens were bound to the MWNT using a diimide-activated amidation process and the immunogen was characterized by TEM, AFM and Raman Spectroscopy. Furthermore, the immunogenicity of this vaccine candidate was evaluated in a murine model. Immunization with MWNT-DENV3E induced comparable IgG responses in relation to the immunization with non-conjugated proteins; however, the inoculation of the nanoconjugate into mice generated higher titers of neutralizing antibodies. Cell-mediated responses were also evaluated, and higher Dengue-specific splenocyte proliferation was observed in cell cultures derived from mice immunized with MWNT-DENV3E when compared to animals immunized with the non-conjugated DENV3E. Despite the recent licensure of the CYD-TDV Dengue vaccine in some countries, results from the vaccine’s phase III trial have cast doubts about its overall efficacy and global applicability. While questions about the effectiveness of the CYD-TDV vaccine still lingers, it is wise to keep at hand an array of vaccine candidates, including alternative non-classical approaches like the one presented here.
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A MVA construct expressing a secretable form of the Dengue Virus 3 envelope protein protects immunized mice from Dengue-induced encephalitis.
Vaccine, 2016Co-Authors: Bárbara Resende Quinan, Alice F. Versiani, Flávio Guimarães Da FonsecaAbstract:Dengue is no longer restricted to tropical developing countries, but is now a major global public health problem. Despite the recent license approval of the CYD-TDV vaccine in some countries, efforts to develop a more efficient vaccine against Dengue Virus (DENV) continue. Herein, we evaluate the immunogenicity and level of protection of two potential vaccines against DENV based on recombinant modified vaccinia Virus Ankara (rMVA). The vaccine addressing the Envelope protein from DENV serotype 3 to the endoplasmic reticulum elicited neutralizing antibodies titers which correlate with protection, and also confers protection upon challenge in a mouse model. Our results support the development of a tetravalent Dengue vaccine with the further construction of rMVAs expressing proteins from the other DENV serotypes.
Milene A. Rachid - One of the best experts on this subject based on the ideXlab platform.
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Multi-walled carbon nanotubes functionalized with recombinant Dengue Virus 3 envelope proteins induce significant and specific immune responses in mice
Journal of Nanobiotechnology, 2017Co-Authors: Alice F. Versiani, Ruiz G. Astigarraga, Eliseu S. O. Rocha, Ana Paula M. Barboza, Erna G. Kroon, Milene A. Rachid, Daniele G. Souza, Luiz O. Ladeira, Edel F. Barbosa-stancioli, Ado JorioAbstract:Background Dengue is the most prevalent arthropod-borne viral disease in the world. In this article we present results on the development, characterization and immunogenic evaluation of an alternative vaccine candidate against Dengue. Methods The MWNT-DENV3E nanoconjugate was developed by covalent functionalization of carboxylated multi-walled carbon nanotubes (MWNT) with recombinant Dengue envelope (DENV3E) proteins. The recombinant antigens were bound to the MWNT using a diimide-activated amidation process and the immunogen was characterized by TEM, AFM and Raman Spectroscopy. Furthermore, the immunogenicity of this vaccine candidate was evaluated in a murine model. Results Immunization with MWNT-DENV3E induced comparable IgG responses in relation to the immunization with non-conjugated proteins; however, the inoculation of the nanoconjugate into mice generated higher titers of neutralizing antibodies. Cell-mediated responses were also evaluated, and higher Dengue-specific splenocyte proliferation was observed in cell cultures derived from mice immunized with MWNT-DENV3E when compared to animals immunized with the non-conjugated DENV3E. Conclusions Despite the recent licensure of the CYD-TDV Dengue vaccine in some countries, results from the vaccine’s phase III trial have cast doubts about its overall efficacy and global applicability. While questions about the effectiveness of the CYD-TDV vaccine still lingers, it is wise to keep at hand an array of vaccine candidates, including alternative non-classical approaches like the one presented here.
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Multi-walled carbon nanotubes functionalized with recombinant Dengue Virus 3 envelope proteins induce significant and specific immune responses in mice.
Journal of nanobiotechnology, 2017Co-Authors: Alice F. Versiani, Erna Geessien Kroon, Ruiz G. Astigarraga, Ana Paula M. Barboza, Milene A. Rachid, Daniele G. Souza, Luiz O. Ladeira, Edel F. Barbosa-stancioli, Eliseu Soares De Oliveira Rocha, Ado JorioAbstract:Dengue is the most prevalent arthropod-borne viral disease in the world. In this article we present results on the development, characterization and immunogenic evaluation of an alternative vaccine candidate against Dengue. The MWNT-DENV3E nanoconjugate was developed by covalent functionalization of carboxylated multi-walled carbon nanotubes (MWNT) with recombinant Dengue envelope (DENV3E) proteins. The recombinant antigens were bound to the MWNT using a diimide-activated amidation process and the immunogen was characterized by TEM, AFM and Raman Spectroscopy. Furthermore, the immunogenicity of this vaccine candidate was evaluated in a murine model. Immunization with MWNT-DENV3E induced comparable IgG responses in relation to the immunization with non-conjugated proteins; however, the inoculation of the nanoconjugate into mice generated higher titers of neutralizing antibodies. Cell-mediated responses were also evaluated, and higher Dengue-specific splenocyte proliferation was observed in cell cultures derived from mice immunized with MWNT-DENV3E when compared to animals immunized with the non-conjugated DENV3E. Despite the recent licensure of the CYD-TDV Dengue vaccine in some countries, results from the vaccine’s phase III trial have cast doubts about its overall efficacy and global applicability. While questions about the effectiveness of the CYD-TDV vaccine still lingers, it is wise to keep at hand an array of vaccine candidates, including alternative non-classical approaches like the one presented here.
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Intracerebral infection with Dengue-3 Virus induces meningoencephalitis and behavioral changes that precede lethality in mice.
Journal of neuroinflammation, 2011Co-Authors: Débora Cristina Guerra Amaral, Gustavo Portela Ferreira, Milene A. Rachid, Marcia C Vilela, David H Rodrigues, Norinne Lacerda-queiroz, Aline S Miranda, Vivian V Costa, Roberta Dayrell De Lima Campos, Marco Antônio CamposAbstract:Dengue, one of the most important arboviral diseases of humans, may cause severe systemic disease. Although Dengue Virus (DENV) has been considered to be a non-neurotropic Virus, Dengue infection has been associated recently with a series of neurological syndromes, including encephalitis. In this work, we evaluated behavioral changes and inflammatory parameters in C57BL/6 mice infected with non-adapted Dengue Virus 3 (DENV-3) genotype I. C57BL/6 mice received 4×10(3) PFU of DENV-3 by an intracranial route. We evaluated the trafficking of leukocytes in brain microvasculature using intravital microscopy, and evaluated chemokine and cytokine profiling by an ELISA test at 3 and 6 days post infection (p.i.). Furthermore, we determined myeloperoxidase activity and immune cell populations, and also performed histopathological analysis and immunostaining for the Virus in brain tissue. All animals developed signs of encephalitis and died by day 8 p.i. Motor behavior and muscle tone and strength parameters declined at day 7 p.i. We observed increased leukocyte rolling and adhesion in brain microvasculature of infected mice at days 3 and 6 p.i. The infection was followed by significant increases in IFN-γ, TNF-α, CCL2, CCL5, CXCL1, and CXCL2. Histological analysis showed evidence of meningoencephalitis and reactive gliosis. Increased numbers of neutrophils, CD4+ and CD8+ T cells were detected in brain of infected animals, notably at day 6 p.i. Cells immunoreactive for anti-NS-3 were visualized throughout the brain. Intracerebral infection with non-adapted DENV-3 induces encephalitis and behavioral changes that precede lethality in mice.