author_facet Brault, Aaron C.
Domi, Arban
McDonald, Erin M.
Talmi-Frank, Dalit
McCurley, Nathanael
Basu, Rahul
Robinson, Harriet L.
Hellerstein, Michael
Duggal, Nisha K.
Bowen, Richard A.
Guirakhoo, Farshad
Brault, Aaron C.
Domi, Arban
McDonald, Erin M.
Talmi-Frank, Dalit
McCurley, Nathanael
Basu, Rahul
Robinson, Harriet L.
Hellerstein, Michael
Duggal, Nisha K.
Bowen, Richard A.
Guirakhoo, Farshad
author Brault, Aaron C.
Domi, Arban
McDonald, Erin M.
Talmi-Frank, Dalit
McCurley, Nathanael
Basu, Rahul
Robinson, Harriet L.
Hellerstein, Michael
Duggal, Nisha K.
Bowen, Richard A.
Guirakhoo, Farshad
spellingShingle Brault, Aaron C.
Domi, Arban
McDonald, Erin M.
Talmi-Frank, Dalit
McCurley, Nathanael
Basu, Rahul
Robinson, Harriet L.
Hellerstein, Michael
Duggal, Nisha K.
Bowen, Richard A.
Guirakhoo, Farshad
Scientific Reports
A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
Multidisciplinary
author_sort brault, aaron c.
spelling Brault, Aaron C. Domi, Arban McDonald, Erin M. Talmi-Frank, Dalit McCurley, Nathanael Basu, Rahul Robinson, Harriet L. Hellerstein, Michael Duggal, Nisha K. Bowen, Richard A. Guirakhoo, Farshad 2045-2322 Springer Science and Business Media LLC Multidisciplinary http://dx.doi.org/10.1038/s41598-017-15039-8 <jats:title>Abstract</jats:title><jats:p>Zika virus (ZIKV) is a mosquito-borne flavivirus that has rapidly extended its geographic range around the world. Its association with abnormal fetal brain development, sexual transmission, and lack of a preventive vaccine have constituted a global health concern. Designing a safe and effective vaccine requires significant caution due to overlapping geographical distribution of ZIKV with dengue virus (DENV) and other flaviviruses, possibly resulting in more severe disease manifestations in flavivirus immune vaccinees such as Antibody-Dependent Enhancement (ADE, a phenomenon involved in pathogenesis of DENV, and a risk associated with ZIKV vaccines using the envelope proteins as immunogens). Here, we describe the development of an alternative vaccine strategy encompassing the expression of ZIKV non-structural-1 (NS1) protein from a clinically proven safe, Modified Vaccinia Ankara (MVA) vector, thus averting the potential risk of ADE associated with structural protein-based ZIKV vaccines. A single intramuscular immunization of immunocompetent mice with the MVA-ZIKV-NS1 vaccine candidate provided robust humoral and cellular responses, and afforded 100% protection against a lethal intracerebral dose of ZIKV (strain MR766). This is the first report of (i) a ZIKV vaccine based on the NS1 protein and (ii) single dose protection against ZIKV using an immunocompetent lethal mouse challenge model.</jats:p> A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model Scientific Reports
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title A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
title_unstemmed A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
title_full A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
title_fullStr A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
title_full_unstemmed A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
title_short A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
title_sort a zika vaccine targeting ns1 protein protects immunocompetent adult mice in a lethal challenge model
topic Multidisciplinary
url http://dx.doi.org/10.1038/s41598-017-15039-8
publishDate 2017
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description <jats:title>Abstract</jats:title><jats:p>Zika virus (ZIKV) is a mosquito-borne flavivirus that has rapidly extended its geographic range around the world. Its association with abnormal fetal brain development, sexual transmission, and lack of a preventive vaccine have constituted a global health concern. Designing a safe and effective vaccine requires significant caution due to overlapping geographical distribution of ZIKV with dengue virus (DENV) and other flaviviruses, possibly resulting in more severe disease manifestations in flavivirus immune vaccinees such as Antibody-Dependent Enhancement (ADE, a phenomenon involved in pathogenesis of DENV, and a risk associated with ZIKV vaccines using the envelope proteins as immunogens). Here, we describe the development of an alternative vaccine strategy encompassing the expression of ZIKV non-structural-1 (NS1) protein from a clinically proven safe, Modified Vaccinia Ankara (MVA) vector, thus averting the potential risk of ADE associated with structural protein-based ZIKV vaccines. A single intramuscular immunization of immunocompetent mice with the MVA-ZIKV-NS1 vaccine candidate provided robust humoral and cellular responses, and afforded 100% protection against a lethal intracerebral dose of ZIKV (strain MR766). This is the first report of (i) a ZIKV vaccine based on the NS1 protein and (ii) single dose protection against ZIKV using an immunocompetent lethal mouse challenge model.</jats:p>
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author Brault, Aaron C., Domi, Arban, McDonald, Erin M., Talmi-Frank, Dalit, McCurley, Nathanael, Basu, Rahul, Robinson, Harriet L., Hellerstein, Michael, Duggal, Nisha K., Bowen, Richard A., Guirakhoo, Farshad
author_facet Brault, Aaron C., Domi, Arban, McDonald, Erin M., Talmi-Frank, Dalit, McCurley, Nathanael, Basu, Rahul, Robinson, Harriet L., Hellerstein, Michael, Duggal, Nisha K., Bowen, Richard A., Guirakhoo, Farshad, Brault, Aaron C., Domi, Arban, McDonald, Erin M., Talmi-Frank, Dalit, McCurley, Nathanael, Basu, Rahul, Robinson, Harriet L., Hellerstein, Michael, Duggal, Nisha K., Bowen, Richard A., Guirakhoo, Farshad
author_sort brault, aaron c.
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description <jats:title>Abstract</jats:title><jats:p>Zika virus (ZIKV) is a mosquito-borne flavivirus that has rapidly extended its geographic range around the world. Its association with abnormal fetal brain development, sexual transmission, and lack of a preventive vaccine have constituted a global health concern. Designing a safe and effective vaccine requires significant caution due to overlapping geographical distribution of ZIKV with dengue virus (DENV) and other flaviviruses, possibly resulting in more severe disease manifestations in flavivirus immune vaccinees such as Antibody-Dependent Enhancement (ADE, a phenomenon involved in pathogenesis of DENV, and a risk associated with ZIKV vaccines using the envelope proteins as immunogens). Here, we describe the development of an alternative vaccine strategy encompassing the expression of ZIKV non-structural-1 (NS1) protein from a clinically proven safe, Modified Vaccinia Ankara (MVA) vector, thus averting the potential risk of ADE associated with structural protein-based ZIKV vaccines. A single intramuscular immunization of immunocompetent mice with the MVA-ZIKV-NS1 vaccine candidate provided robust humoral and cellular responses, and afforded 100% protection against a lethal intracerebral dose of ZIKV (strain MR766). This is the first report of (i) a ZIKV vaccine based on the NS1 protein and (ii) single dose protection against ZIKV using an immunocompetent lethal mouse challenge model.</jats:p>
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spelling Brault, Aaron C. Domi, Arban McDonald, Erin M. Talmi-Frank, Dalit McCurley, Nathanael Basu, Rahul Robinson, Harriet L. Hellerstein, Michael Duggal, Nisha K. Bowen, Richard A. Guirakhoo, Farshad 2045-2322 Springer Science and Business Media LLC Multidisciplinary http://dx.doi.org/10.1038/s41598-017-15039-8 <jats:title>Abstract</jats:title><jats:p>Zika virus (ZIKV) is a mosquito-borne flavivirus that has rapidly extended its geographic range around the world. Its association with abnormal fetal brain development, sexual transmission, and lack of a preventive vaccine have constituted a global health concern. Designing a safe and effective vaccine requires significant caution due to overlapping geographical distribution of ZIKV with dengue virus (DENV) and other flaviviruses, possibly resulting in more severe disease manifestations in flavivirus immune vaccinees such as Antibody-Dependent Enhancement (ADE, a phenomenon involved in pathogenesis of DENV, and a risk associated with ZIKV vaccines using the envelope proteins as immunogens). Here, we describe the development of an alternative vaccine strategy encompassing the expression of ZIKV non-structural-1 (NS1) protein from a clinically proven safe, Modified Vaccinia Ankara (MVA) vector, thus averting the potential risk of ADE associated with structural protein-based ZIKV vaccines. A single intramuscular immunization of immunocompetent mice with the MVA-ZIKV-NS1 vaccine candidate provided robust humoral and cellular responses, and afforded 100% protection against a lethal intracerebral dose of ZIKV (strain MR766). This is the first report of (i) a ZIKV vaccine based on the NS1 protein and (ii) single dose protection against ZIKV using an immunocompetent lethal mouse challenge model.</jats:p> A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model Scientific Reports
spellingShingle Brault, Aaron C., Domi, Arban, McDonald, Erin M., Talmi-Frank, Dalit, McCurley, Nathanael, Basu, Rahul, Robinson, Harriet L., Hellerstein, Michael, Duggal, Nisha K., Bowen, Richard A., Guirakhoo, Farshad, Scientific Reports, A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model, Multidisciplinary
title A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
title_full A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
title_fullStr A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
title_full_unstemmed A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
title_short A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
title_sort a zika vaccine targeting ns1 protein protects immunocompetent adult mice in a lethal challenge model
title_unstemmed A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model
topic Multidisciplinary
url http://dx.doi.org/10.1038/s41598-017-15039-8