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Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials
BACKGROUND: The Zika virus epidemic and associated congenital infections have prompted rapid vaccine development. We assessed two new DNA vaccines expressing premembrane and envelope Zika virus structural proteins. METHODS: We did two phase 1, randomised, open-label trials involving healthy adult vo...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Ltd.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379903/ https://www.ncbi.nlm.nih.gov/pubmed/29217376 http://dx.doi.org/10.1016/S0140-6736(17)33105-7 |
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author | Gaudinski, Martin R Houser, Katherine V Morabito, Kaitlyn M Hu, Zonghui Yamshchikov, Galina Rothwell, Ro Shauna Berkowitz, Nina Mendoza, Floreliz Saunders, Jamie G Novik, Laura Hendel, Cynthia S Holman, LaSonji A Gordon, Ingelise J Cox, Josephine H Edupuganti, Srilatha McArthur, Monica A Rouphael, Nadine G Lyke, Kirsten E Cummings, Ginny E Sitar, Sandra Bailer, Robert T Foreman, Bryant M Burgomaster, Katherine Pelc, Rebecca S Gordon, David N DeMaso, Christina R Dowd, Kimberly A Laurencot, Carolyn Schwartz, Richard M Mascola, John R Graham, Barney S Pierson, Theodore C Ledgerwood, Julie E Chen, Grace L |
author_facet | Gaudinski, Martin R Houser, Katherine V Morabito, Kaitlyn M Hu, Zonghui Yamshchikov, Galina Rothwell, Ro Shauna Berkowitz, Nina Mendoza, Floreliz Saunders, Jamie G Novik, Laura Hendel, Cynthia S Holman, LaSonji A Gordon, Ingelise J Cox, Josephine H Edupuganti, Srilatha McArthur, Monica A Rouphael, Nadine G Lyke, Kirsten E Cummings, Ginny E Sitar, Sandra Bailer, Robert T Foreman, Bryant M Burgomaster, Katherine Pelc, Rebecca S Gordon, David N DeMaso, Christina R Dowd, Kimberly A Laurencot, Carolyn Schwartz, Richard M Mascola, John R Graham, Barney S Pierson, Theodore C Ledgerwood, Julie E Chen, Grace L |
author_sort | Gaudinski, Martin R |
collection | PubMed |
description | BACKGROUND: The Zika virus epidemic and associated congenital infections have prompted rapid vaccine development. We assessed two new DNA vaccines expressing premembrane and envelope Zika virus structural proteins. METHODS: We did two phase 1, randomised, open-label trials involving healthy adult volunteers. The VRC 319 trial, done in three centres, assessed plasmid VRC5288 (Zika virus and Japanese encephalitis virus chimera), and the VRC 320, done in one centre, assessed plasmid VRC5283 (wild-type Zika virus). Eligible participants were aged 18–35 years in VRC19 and 18–50 years in VRC 320. Participants were randomly assigned 1:1 by a computer-generated randomisation schedule prepared by the study statistician. All participants received intramuscular injection of 4 mg vaccine. In VRC 319 participants were assigned to receive vaccinations via needle and syringe at 0 and 8 weeks, 0 and 12 weeks, 0, 4, and 8 weeks, or 0, 4, and 20 weeks. In VRC 320 participants were assigned to receive vaccinations at 0, 4, and 8 weeks via single-dose needle and syringe injection in one deltoid or split-dose needle and syringe or needle-free injection with the Stratis device (Pharmajet, Golden, CO, USA) in each deltoid. Both trials followed up volunteers for 24 months for the primary endpoint of safety, assessed as local and systemic reactogenicity in the 7 days after each vaccination and all adverse events in the 28 days after each vaccination. The secondary endpoint in both trials was immunogenicity 4 weeks after last vaccination. These trials are registered with ClinicalTrials.gov, numbers NCT02840487 and NCT02996461. FINDINGS: VRC 319 enrolled 80 participants (20 in each group), and VRC 320 enrolled 45 participants (15 in each group). One participant in VRC 319 and two in VRC 320 withdrew after one dose of vaccine, but were included in the safety analyses. Both vaccines were safe and well tolerated. All local and systemic symptoms were mild to moderate. In both studies, pain and tenderness at the injection site was the most frequent local symptoms (37 [46%] of 80 participants in VRC 319 and 36 [80%] of 45 in VRC 320) and malaise and headache were the most frequent systemic symptoms (22 [27%] and 18 [22%], respectively, in VRC 319 and 17 [38%] and 15 [33%], respectively, in VRC 320). For VRC5283, 14 of 14 (100%) participants who received split-dose vaccinations by needle-free injection had detectable positive antibody responses, and the geometric mean titre of 304 was the highest across all groups in both trials. INTERPRETATION: VRC5283 was well tolerated and has advanced to phase 2 efficacy testing. FUNDING: Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health. |
format | Online Article Text |
id | pubmed-6379903 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63799032019-02-19 Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials Gaudinski, Martin R Houser, Katherine V Morabito, Kaitlyn M Hu, Zonghui Yamshchikov, Galina Rothwell, Ro Shauna Berkowitz, Nina Mendoza, Floreliz Saunders, Jamie G Novik, Laura Hendel, Cynthia S Holman, LaSonji A Gordon, Ingelise J Cox, Josephine H Edupuganti, Srilatha McArthur, Monica A Rouphael, Nadine G Lyke, Kirsten E Cummings, Ginny E Sitar, Sandra Bailer, Robert T Foreman, Bryant M Burgomaster, Katherine Pelc, Rebecca S Gordon, David N DeMaso, Christina R Dowd, Kimberly A Laurencot, Carolyn Schwartz, Richard M Mascola, John R Graham, Barney S Pierson, Theodore C Ledgerwood, Julie E Chen, Grace L Lancet Article BACKGROUND: The Zika virus epidemic and associated congenital infections have prompted rapid vaccine development. We assessed two new DNA vaccines expressing premembrane and envelope Zika virus structural proteins. METHODS: We did two phase 1, randomised, open-label trials involving healthy adult volunteers. The VRC 319 trial, done in three centres, assessed plasmid VRC5288 (Zika virus and Japanese encephalitis virus chimera), and the VRC 320, done in one centre, assessed plasmid VRC5283 (wild-type Zika virus). Eligible participants were aged 18–35 years in VRC19 and 18–50 years in VRC 320. Participants were randomly assigned 1:1 by a computer-generated randomisation schedule prepared by the study statistician. All participants received intramuscular injection of 4 mg vaccine. In VRC 319 participants were assigned to receive vaccinations via needle and syringe at 0 and 8 weeks, 0 and 12 weeks, 0, 4, and 8 weeks, or 0, 4, and 20 weeks. In VRC 320 participants were assigned to receive vaccinations at 0, 4, and 8 weeks via single-dose needle and syringe injection in one deltoid or split-dose needle and syringe or needle-free injection with the Stratis device (Pharmajet, Golden, CO, USA) in each deltoid. Both trials followed up volunteers for 24 months for the primary endpoint of safety, assessed as local and systemic reactogenicity in the 7 days after each vaccination and all adverse events in the 28 days after each vaccination. The secondary endpoint in both trials was immunogenicity 4 weeks after last vaccination. These trials are registered with ClinicalTrials.gov, numbers NCT02840487 and NCT02996461. FINDINGS: VRC 319 enrolled 80 participants (20 in each group), and VRC 320 enrolled 45 participants (15 in each group). One participant in VRC 319 and two in VRC 320 withdrew after one dose of vaccine, but were included in the safety analyses. Both vaccines were safe and well tolerated. All local and systemic symptoms were mild to moderate. In both studies, pain and tenderness at the injection site was the most frequent local symptoms (37 [46%] of 80 participants in VRC 319 and 36 [80%] of 45 in VRC 320) and malaise and headache were the most frequent systemic symptoms (22 [27%] and 18 [22%], respectively, in VRC 319 and 17 [38%] and 15 [33%], respectively, in VRC 320). For VRC5283, 14 of 14 (100%) participants who received split-dose vaccinations by needle-free injection had detectable positive antibody responses, and the geometric mean titre of 304 was the highest across all groups in both trials. INTERPRETATION: VRC5283 was well tolerated and has advanced to phase 2 efficacy testing. FUNDING: Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Elsevier Ltd. 2018 2017-12-05 /pmc/articles/PMC6379903/ /pubmed/29217376 http://dx.doi.org/10.1016/S0140-6736(17)33105-7 Text en © 2017 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Gaudinski, Martin R Houser, Katherine V Morabito, Kaitlyn M Hu, Zonghui Yamshchikov, Galina Rothwell, Ro Shauna Berkowitz, Nina Mendoza, Floreliz Saunders, Jamie G Novik, Laura Hendel, Cynthia S Holman, LaSonji A Gordon, Ingelise J Cox, Josephine H Edupuganti, Srilatha McArthur, Monica A Rouphael, Nadine G Lyke, Kirsten E Cummings, Ginny E Sitar, Sandra Bailer, Robert T Foreman, Bryant M Burgomaster, Katherine Pelc, Rebecca S Gordon, David N DeMaso, Christina R Dowd, Kimberly A Laurencot, Carolyn Schwartz, Richard M Mascola, John R Graham, Barney S Pierson, Theodore C Ledgerwood, Julie E Chen, Grace L Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials |
title | Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials |
title_full | Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials |
title_fullStr | Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials |
title_full_unstemmed | Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials |
title_short | Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials |
title_sort | safety, tolerability, and immunogenicity of two zika virus dna vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379903/ https://www.ncbi.nlm.nih.gov/pubmed/29217376 http://dx.doi.org/10.1016/S0140-6736(17)33105-7 |
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