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Safety and Immunogenicity of a DNA SARS-CoV-2 vaccine (ZyCoV-D): Results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India

BACKGROUND: ZyCoV-D is a DNA vaccine candidate, which comprises a plasmid DNA carrying spike-S gene of SARS-CoV-2 virus along with gene coding for signal peptide. The spike(S) region includes the receptor-binding domain (RBD), which binds to the human angiotensin converting Enzyme (ACE)-2 receptor a...

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Autores principales: Momin, Taufik, Kansagra, Kevinkumar, Patel, Hardik, Sharma, Sunil, Sharma, Bhumika, Patel, Jatin, Mittal, Ravindra, Sanmukhani, Jayesh, Maithal, Kapil, Dey, Ayan, Chandra, Harish, Rajanathan, Chozhavel TM, Pericherla, Hari PR, Kumar, Pawan, Narkhede, Anjali, Parmar, Deven
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285262/
https://www.ncbi.nlm.nih.gov/pubmed/34308319
http://dx.doi.org/10.1016/j.eclinm.2021.101020
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author Momin, Taufik
Kansagra, Kevinkumar
Patel, Hardik
Sharma, Sunil
Sharma, Bhumika
Patel, Jatin
Mittal, Ravindra
Sanmukhani, Jayesh
Maithal, Kapil
Dey, Ayan
Chandra, Harish
Rajanathan, Chozhavel TM
Pericherla, Hari PR
Kumar, Pawan
Narkhede, Anjali
Parmar, Deven
author_facet Momin, Taufik
Kansagra, Kevinkumar
Patel, Hardik
Sharma, Sunil
Sharma, Bhumika
Patel, Jatin
Mittal, Ravindra
Sanmukhani, Jayesh
Maithal, Kapil
Dey, Ayan
Chandra, Harish
Rajanathan, Chozhavel TM
Pericherla, Hari PR
Kumar, Pawan
Narkhede, Anjali
Parmar, Deven
author_sort Momin, Taufik
collection PubMed
description BACKGROUND: ZyCoV-D is a DNA vaccine candidate, which comprises a plasmid DNA carrying spike-S gene of SARS-CoV-2 virus along with gene coding for signal peptide. The spike(S) region includes the receptor-binding domain (RBD), which binds to the human angiotensin converting Enzyme (ACE)-2 receptor and mediates the entry of virus inside the cell. METHODS: We conducted a single-center, open-label, non-randomized, Phase 1 trial in India between July 2020 and October 2020. Healthy adults aged between 18 and 55 years were sequentially enrolled and allocated to one of four treatment arms in a dose escalation manner. Three doses of vaccine were administered 28 days apart and each subject was followed up for 28 days post third dose to evaluate safety and immunogenicity. FINDINGS: Out of 126 individuals screened for eligibility. Forty-eight subjects (mean age 34·9 years) were enrolled and vaccinated in the Phase 1 study Overall, 12/48 (25%) subjects reported at least one AE (i.e. combined solicited and unsolicited) during the study. There were no deaths or serious adverse events reported in Phase 1 of the study. The proportion of subjects who seroconverted based on IgG titers on day 84 was 4/11 (36·36%), 4/12 (33·33%), 10/10 (100·00%) and 8/10 (80·00%) in the treatment Arm 1 (1 mg: Needle), Arm 2 (1 mg: NFIS), Arm 3 (2 mg: Needle) and Arm 4 (2 mg: NFIS), respectively. INTERPRETATION: ZyCoV-D vaccine is found to be safe, well-tolerated and immunogenic in the Phase 1 trial. Our findings suggest that the DNA vaccine warrants further investigation.
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spelling pubmed-82852622021-07-20 Safety and Immunogenicity of a DNA SARS-CoV-2 vaccine (ZyCoV-D): Results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India Momin, Taufik Kansagra, Kevinkumar Patel, Hardik Sharma, Sunil Sharma, Bhumika Patel, Jatin Mittal, Ravindra Sanmukhani, Jayesh Maithal, Kapil Dey, Ayan Chandra, Harish Rajanathan, Chozhavel TM Pericherla, Hari PR Kumar, Pawan Narkhede, Anjali Parmar, Deven EClinicalMedicine Research Paper BACKGROUND: ZyCoV-D is a DNA vaccine candidate, which comprises a plasmid DNA carrying spike-S gene of SARS-CoV-2 virus along with gene coding for signal peptide. The spike(S) region includes the receptor-binding domain (RBD), which binds to the human angiotensin converting Enzyme (ACE)-2 receptor and mediates the entry of virus inside the cell. METHODS: We conducted a single-center, open-label, non-randomized, Phase 1 trial in India between July 2020 and October 2020. Healthy adults aged between 18 and 55 years were sequentially enrolled and allocated to one of four treatment arms in a dose escalation manner. Three doses of vaccine were administered 28 days apart and each subject was followed up for 28 days post third dose to evaluate safety and immunogenicity. FINDINGS: Out of 126 individuals screened for eligibility. Forty-eight subjects (mean age 34·9 years) were enrolled and vaccinated in the Phase 1 study Overall, 12/48 (25%) subjects reported at least one AE (i.e. combined solicited and unsolicited) during the study. There were no deaths or serious adverse events reported in Phase 1 of the study. The proportion of subjects who seroconverted based on IgG titers on day 84 was 4/11 (36·36%), 4/12 (33·33%), 10/10 (100·00%) and 8/10 (80·00%) in the treatment Arm 1 (1 mg: Needle), Arm 2 (1 mg: NFIS), Arm 3 (2 mg: Needle) and Arm 4 (2 mg: NFIS), respectively. INTERPRETATION: ZyCoV-D vaccine is found to be safe, well-tolerated and immunogenic in the Phase 1 trial. Our findings suggest that the DNA vaccine warrants further investigation. Elsevier 2021-07-17 /pmc/articles/PMC8285262/ /pubmed/34308319 http://dx.doi.org/10.1016/j.eclinm.2021.101020 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Momin, Taufik
Kansagra, Kevinkumar
Patel, Hardik
Sharma, Sunil
Sharma, Bhumika
Patel, Jatin
Mittal, Ravindra
Sanmukhani, Jayesh
Maithal, Kapil
Dey, Ayan
Chandra, Harish
Rajanathan, Chozhavel TM
Pericherla, Hari PR
Kumar, Pawan
Narkhede, Anjali
Parmar, Deven
Safety and Immunogenicity of a DNA SARS-CoV-2 vaccine (ZyCoV-D): Results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India
title Safety and Immunogenicity of a DNA SARS-CoV-2 vaccine (ZyCoV-D): Results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India
title_full Safety and Immunogenicity of a DNA SARS-CoV-2 vaccine (ZyCoV-D): Results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India
title_fullStr Safety and Immunogenicity of a DNA SARS-CoV-2 vaccine (ZyCoV-D): Results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India
title_full_unstemmed Safety and Immunogenicity of a DNA SARS-CoV-2 vaccine (ZyCoV-D): Results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India
title_short Safety and Immunogenicity of a DNA SARS-CoV-2 vaccine (ZyCoV-D): Results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India
title_sort safety and immunogenicity of a dna sars-cov-2 vaccine (zycov-d): results of an open-label, non-randomized phase i part of phase i/ii clinical study by intradermal route in healthy subjects in india
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285262/
https://www.ncbi.nlm.nih.gov/pubmed/34308319
http://dx.doi.org/10.1016/j.eclinm.2021.101020
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