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ZIKA-001: Safety and Immunogenicity of an Engineered DNA Vaccine Against ZIKA virus infection
BACKGROUND: While Zika virus (ZIKV) infection is typically self-limited, congenital birth defects and Guillain-Barré syndrome are well-described. There are no therapies or vaccines against ZIKV infection. METHODS: ZIKA-001 is a phase I, open label, clinical trial designed to evaluate the safety, sid...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5631827/ http://dx.doi.org/10.1093/ofid/ofx163.693 |
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author | Tebas, Pablo Roberts, Christine C Muthumani, Kar Reuschel, Emma White, Scott Khan, Amir S Racine, Trina Choi, Hyeree Zaidi, Faraz Boyer, Jean Kudchodkar, Sagar Park, Young K Trottier, Sylvie Remigio, Celine Krieger, Diane Kobinger, Gary P Weiner, David Maslow, Joel |
author_facet | Tebas, Pablo Roberts, Christine C Muthumani, Kar Reuschel, Emma White, Scott Khan, Amir S Racine, Trina Choi, Hyeree Zaidi, Faraz Boyer, Jean Kudchodkar, Sagar Park, Young K Trottier, Sylvie Remigio, Celine Krieger, Diane Kobinger, Gary P Weiner, David Maslow, Joel |
author_sort | Tebas, Pablo |
collection | PubMed |
description | BACKGROUND: While Zika virus (ZIKV) infection is typically self-limited, congenital birth defects and Guillain-Barré syndrome are well-described. There are no therapies or vaccines against ZIKV infection. METHODS: ZIKA-001 is a phase I, open label, clinical trial designed to evaluate the safety, side effect profile, and immunogenicity of a synthetic, DNA vaccine (GLS-5700) targeting the pre-membrane+envelope proteins (prME) of the virus. Two groups of 20 participants received GLS-5700 at one of two dose levels: 1 mg or 2 mg DNA/dose at 0, 4, and 12 weeks. Vaccine was administered as 0.1 or 0.2 ml (1 or 2 mg) intradermal (ID) injection followed by electroporation (EP) with the CELLECTRA(®)-3P device RESULTS: The median age of the 40 participants was 38 (IQR 30–54) years; 60% were female 30% Latino and 78% white. No SAEs have been reported to date. Local minor AEs were injection site pain, redness, swelling and itching that occurred in half of the participants. Systemic adverse events were rare and included headache, myalgias, upper respiratory infections, fatigue/malaise and nausea. Four weeks after the first dose 25% vs. 60% of the participants in the 1 mg and 2 mg dose seroconverted. By week 6, 2 weeks after the second dose, the response was 65 and 84% respectively and 2 weeks after the third dose all participants in both dosing groups developed antibodies. At the end of the vaccination period over 60% of vaccinated person neutralized Zika virus in a vero cell assay and greater than 80% on neuronal cell targets. The protective efficacy of the antibodies generated by the vaccine was evaluated in the lethal IFNAR−/− mouse model. After the intraperitoneal administration of 0.1 ml of either baseline, week 14 serum or PBS the animals were challenged with 10(6) PFUs of ZIKV PR209 isolate. Whereas animals administered PBS (control) or baseline serum succumbed after a median of 5 days, those pretreated with week 14 serum from study participants survived suggesting that the humoral response generated by the vaccine is protective in this model. CONCLUSION: Our trial shows for the first time in humans the safety and immunogenicity of an engineered DNA encoding consensus viral protein against ZIKV. Future studies will evaluate the effectiveness of the vaccine. DISCLOSURES: C. C. Roberts, GeneOne: Member, Salary. S. White, GeneOne: Member, Salary. A. S. Khan, Inovio: Employee and Shareholder, Salary and Stock. J. Boyer, Inovio: Employee and Shareholder, Salary and Stock. Y. K. Park, GeneOne: Board Member, CEO and Employee, Salary and Stock. S. Trottier, Canadian Institutes of Health Research: Investigator, Research grant. C. Remigio, GeneOne: Employee and Shareholder, Salary and Stock. G. P. Kobinger, GeneOne: Grant Investigator and Scientific Advisor, Grant recipient and Research support. D. Weiner, GeneOne: Grant Investigator and Scientific Advisor, Grant recipient, Licensing agreement or royalty and Stock. J. Maslow, GeneOne: Employee, Salary and Stock. |
format | Online Article Text |
id | pubmed-5631827 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-56318272017-11-07 ZIKA-001: Safety and Immunogenicity of an Engineered DNA Vaccine Against ZIKA virus infection Tebas, Pablo Roberts, Christine C Muthumani, Kar Reuschel, Emma White, Scott Khan, Amir S Racine, Trina Choi, Hyeree Zaidi, Faraz Boyer, Jean Kudchodkar, Sagar Park, Young K Trottier, Sylvie Remigio, Celine Krieger, Diane Kobinger, Gary P Weiner, David Maslow, Joel Open Forum Infect Dis Abstracts BACKGROUND: While Zika virus (ZIKV) infection is typically self-limited, congenital birth defects and Guillain-Barré syndrome are well-described. There are no therapies or vaccines against ZIKV infection. METHODS: ZIKA-001 is a phase I, open label, clinical trial designed to evaluate the safety, side effect profile, and immunogenicity of a synthetic, DNA vaccine (GLS-5700) targeting the pre-membrane+envelope proteins (prME) of the virus. Two groups of 20 participants received GLS-5700 at one of two dose levels: 1 mg or 2 mg DNA/dose at 0, 4, and 12 weeks. Vaccine was administered as 0.1 or 0.2 ml (1 or 2 mg) intradermal (ID) injection followed by electroporation (EP) with the CELLECTRA(®)-3P device RESULTS: The median age of the 40 participants was 38 (IQR 30–54) years; 60% were female 30% Latino and 78% white. No SAEs have been reported to date. Local minor AEs were injection site pain, redness, swelling and itching that occurred in half of the participants. Systemic adverse events were rare and included headache, myalgias, upper respiratory infections, fatigue/malaise and nausea. Four weeks after the first dose 25% vs. 60% of the participants in the 1 mg and 2 mg dose seroconverted. By week 6, 2 weeks after the second dose, the response was 65 and 84% respectively and 2 weeks after the third dose all participants in both dosing groups developed antibodies. At the end of the vaccination period over 60% of vaccinated person neutralized Zika virus in a vero cell assay and greater than 80% on neuronal cell targets. The protective efficacy of the antibodies generated by the vaccine was evaluated in the lethal IFNAR−/− mouse model. After the intraperitoneal administration of 0.1 ml of either baseline, week 14 serum or PBS the animals were challenged with 10(6) PFUs of ZIKV PR209 isolate. Whereas animals administered PBS (control) or baseline serum succumbed after a median of 5 days, those pretreated with week 14 serum from study participants survived suggesting that the humoral response generated by the vaccine is protective in this model. CONCLUSION: Our trial shows for the first time in humans the safety and immunogenicity of an engineered DNA encoding consensus viral protein against ZIKV. Future studies will evaluate the effectiveness of the vaccine. DISCLOSURES: C. C. Roberts, GeneOne: Member, Salary. S. White, GeneOne: Member, Salary. A. S. Khan, Inovio: Employee and Shareholder, Salary and Stock. J. Boyer, Inovio: Employee and Shareholder, Salary and Stock. Y. K. Park, GeneOne: Board Member, CEO and Employee, Salary and Stock. S. Trottier, Canadian Institutes of Health Research: Investigator, Research grant. C. Remigio, GeneOne: Employee and Shareholder, Salary and Stock. G. P. Kobinger, GeneOne: Grant Investigator and Scientific Advisor, Grant recipient and Research support. D. Weiner, GeneOne: Grant Investigator and Scientific Advisor, Grant recipient, Licensing agreement or royalty and Stock. J. Maslow, GeneOne: Employee, Salary and Stock. Oxford University Press 2017-10-04 /pmc/articles/PMC5631827/ http://dx.doi.org/10.1093/ofid/ofx163.693 Text en © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Abstracts Tebas, Pablo Roberts, Christine C Muthumani, Kar Reuschel, Emma White, Scott Khan, Amir S Racine, Trina Choi, Hyeree Zaidi, Faraz Boyer, Jean Kudchodkar, Sagar Park, Young K Trottier, Sylvie Remigio, Celine Krieger, Diane Kobinger, Gary P Weiner, David Maslow, Joel ZIKA-001: Safety and Immunogenicity of an Engineered DNA Vaccine Against ZIKA virus infection |
title | ZIKA-001: Safety and Immunogenicity of an Engineered DNA Vaccine Against ZIKA virus infection |
title_full | ZIKA-001: Safety and Immunogenicity of an Engineered DNA Vaccine Against ZIKA virus infection |
title_fullStr | ZIKA-001: Safety and Immunogenicity of an Engineered DNA Vaccine Against ZIKA virus infection |
title_full_unstemmed | ZIKA-001: Safety and Immunogenicity of an Engineered DNA Vaccine Against ZIKA virus infection |
title_short | ZIKA-001: Safety and Immunogenicity of an Engineered DNA Vaccine Against ZIKA virus infection |
title_sort | zika-001: safety and immunogenicity of an engineered dna vaccine against zika virus infection |
topic | Abstracts |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5631827/ http://dx.doi.org/10.1093/ofid/ofx163.693 |
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