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Safety and immunogenicity of a synthetic multiantigen modified vaccinia virus Ankara-based COVID-19 vaccine (COH04S1): an open-label and randomised, phase 1 trial

BACKGROUND: COH04S1, a synthetic attenuated modified vaccinia virus Ankara vector co-expressing SARS-CoV-2 spike and nucleocapsid antigens, was tested for safety and immunogenicity in healthy adults. METHODS: This combined open-label and randomised, phase 1 trial was done at the City of Hope Compreh...

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Autores principales: Chiuppesi, Flavia, Zaia, John A, Frankel, Paul H, Stan, Rodica, Drake, Jennifer, Williams, Brenda, Acosta, Anne Marie, Francis, Karyn, Taplitz, Randy A, Dickter, Janet K, Dadwal, Sanjeet, Puing, Alfredo G, Nanayakkara, Deepa D, Ash, Patricia, Cui, Yujie, Contreras, Heidi, La Rosa, Corinna, Tiemann, Katrin, Park, Yoonsuh, Medina, Joybelle, Iniguez, Angelina, Zhou, Qiao, Karpinski, Veronica, Johnson, Daisy, Faircloth, Katelyn, Kaltcheva, Teadora, Nguyen, Jenny, Kha, Mindy, Nguyen, Vu H, Francisco, Sandra Ortega, Grifoni, Alba, Wong, Angela, Sette, Alessandro, Wussow, Felix, Diamond, Don J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Author(s). Published by Elsevier Ltd. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906816/
https://www.ncbi.nlm.nih.gov/pubmed/35287430
http://dx.doi.org/10.1016/S2666-5247(22)00027-1
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author Chiuppesi, Flavia
Zaia, John A
Frankel, Paul H
Stan, Rodica
Drake, Jennifer
Williams, Brenda
Acosta, Anne Marie
Francis, Karyn
Taplitz, Randy A
Dickter, Janet K
Dadwal, Sanjeet
Puing, Alfredo G
Nanayakkara, Deepa D
Ash, Patricia
Cui, Yujie
Contreras, Heidi
La Rosa, Corinna
Tiemann, Katrin
Park, Yoonsuh
Medina, Joybelle
Iniguez, Angelina
Zhou, Qiao
Karpinski, Veronica
Johnson, Daisy
Faircloth, Katelyn
Kaltcheva, Teadora
Nguyen, Jenny
Kha, Mindy
Nguyen, Vu H
Francisco, Sandra Ortega
Grifoni, Alba
Wong, Angela
Sette, Alessandro
Wussow, Felix
Diamond, Don J
author_facet Chiuppesi, Flavia
Zaia, John A
Frankel, Paul H
Stan, Rodica
Drake, Jennifer
Williams, Brenda
Acosta, Anne Marie
Francis, Karyn
Taplitz, Randy A
Dickter, Janet K
Dadwal, Sanjeet
Puing, Alfredo G
Nanayakkara, Deepa D
Ash, Patricia
Cui, Yujie
Contreras, Heidi
La Rosa, Corinna
Tiemann, Katrin
Park, Yoonsuh
Medina, Joybelle
Iniguez, Angelina
Zhou, Qiao
Karpinski, Veronica
Johnson, Daisy
Faircloth, Katelyn
Kaltcheva, Teadora
Nguyen, Jenny
Kha, Mindy
Nguyen, Vu H
Francisco, Sandra Ortega
Grifoni, Alba
Wong, Angela
Sette, Alessandro
Wussow, Felix
Diamond, Don J
author_sort Chiuppesi, Flavia
collection PubMed
description BACKGROUND: COH04S1, a synthetic attenuated modified vaccinia virus Ankara vector co-expressing SARS-CoV-2 spike and nucleocapsid antigens, was tested for safety and immunogenicity in healthy adults. METHODS: This combined open-label and randomised, phase 1 trial was done at the City of Hope Comprehensive Cancer Center (Duarte, CA, USA). We included participants aged 18–54 years with a negative SARS-CoV-2 antibody and PCR test, normal haematology and chemistry panels, a normal electrocardiogram and troponin concentration, negative pregnancy test if female, body-mass index of 30 kg/m(2) or less, and no modified vaccinia virus Ankara or poxvirus vaccine in the past 12 months. In the open-label cohort, 1·0 × 10(7) plaque-forming units (PFU; low dose), 1·0 × 10(8) PFU (medium dose), and 2·5 × 10(8) PFU (high dose) of COH04S1 were administered by intramuscular injection on day 0 and 28 to sentinel participants using a queue-based statistical design to limit risk. In a randomised dose expansion cohort, additional participants were randomly assigned (3:3:1), using block size of seven, to receive two placebo vaccines (placebo group), one low-dose COH04S1 and one placebo vaccine (low-dose COH04S1 plus placebo group), or two low-dose COH04S1 vaccines (low-dose COH04S1 group). The primary outcome was safety and tolerability, with secondary objectives assessing vaccine-specific immunogenicity. The primary immunological outcome was a four times increase (seroconversion) from baseline in spike-specific or nucleocapsid-specific IgG titres within 28 days of the last injection, and seroconversion rates were compared with participants who received placebo using Fisher's exact test. Additional secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ClinicalTrials.gov, NCT046339466. FINDINGS: Between Dec 13, 2020, and May 24, 2021, 56 participants initiated vaccination. On day 0 and 28, 17 participants received low-dose COH04S1, eight received medium-dose COH04S1, nine received high-dose COH04S1, five received placebo, 13 received low-dose COH04S1 followed by placebo, and four discontinued early. Grade 3 fever was observed in one participant who received low-dose COH04S1 and placebo, and grade 2 anxiety or fatigue was seen in one participant who received medium-dose COH04S1. No severe adverse events were reported. Seroconversion was observed in all 34 participants for spike protein and 32 (94%) for nucleocapsid protein (p<0·0001 vs placebo for each comparison). Four times or more increase in SARS-CoV-2 neutralising antibodies within 56 days was measured in nine of 17 participants in the low-dose COH04S1 group, all eight participants in the medium-dose COH04S1 group, and eight of nine participants in the high-dose COH04S1 group (p=0·0035 combined dose levels vs placebo). Post-prime and post-boost four times increase in spike-specific or nucleocapsid-specific T cells secreting interferon-γ was measured in 48 (98%; 95% CI 89–100) of 49 participants who received at least one dose of COH04S1 and provided a sample for immunological analysis. INTERPRETATION: COH04S1 was well tolerated and induced spike-specific and nucleocapsid-specific antibody and T-cell responses. Future evaluation of this COVID-19 vaccine candidate as a primary or boost vaccination is warranted. FUNDING: The Carol Moss Foundation and City of Hope Integrated Drug Development Venture programme.
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spelling pubmed-89068162022-03-10 Safety and immunogenicity of a synthetic multiantigen modified vaccinia virus Ankara-based COVID-19 vaccine (COH04S1): an open-label and randomised, phase 1 trial Chiuppesi, Flavia Zaia, John A Frankel, Paul H Stan, Rodica Drake, Jennifer Williams, Brenda Acosta, Anne Marie Francis, Karyn Taplitz, Randy A Dickter, Janet K Dadwal, Sanjeet Puing, Alfredo G Nanayakkara, Deepa D Ash, Patricia Cui, Yujie Contreras, Heidi La Rosa, Corinna Tiemann, Katrin Park, Yoonsuh Medina, Joybelle Iniguez, Angelina Zhou, Qiao Karpinski, Veronica Johnson, Daisy Faircloth, Katelyn Kaltcheva, Teadora Nguyen, Jenny Kha, Mindy Nguyen, Vu H Francisco, Sandra Ortega Grifoni, Alba Wong, Angela Sette, Alessandro Wussow, Felix Diamond, Don J Lancet Microbe Articles BACKGROUND: COH04S1, a synthetic attenuated modified vaccinia virus Ankara vector co-expressing SARS-CoV-2 spike and nucleocapsid antigens, was tested for safety and immunogenicity in healthy adults. METHODS: This combined open-label and randomised, phase 1 trial was done at the City of Hope Comprehensive Cancer Center (Duarte, CA, USA). We included participants aged 18–54 years with a negative SARS-CoV-2 antibody and PCR test, normal haematology and chemistry panels, a normal electrocardiogram and troponin concentration, negative pregnancy test if female, body-mass index of 30 kg/m(2) or less, and no modified vaccinia virus Ankara or poxvirus vaccine in the past 12 months. In the open-label cohort, 1·0 × 10(7) plaque-forming units (PFU; low dose), 1·0 × 10(8) PFU (medium dose), and 2·5 × 10(8) PFU (high dose) of COH04S1 were administered by intramuscular injection on day 0 and 28 to sentinel participants using a queue-based statistical design to limit risk. In a randomised dose expansion cohort, additional participants were randomly assigned (3:3:1), using block size of seven, to receive two placebo vaccines (placebo group), one low-dose COH04S1 and one placebo vaccine (low-dose COH04S1 plus placebo group), or two low-dose COH04S1 vaccines (low-dose COH04S1 group). The primary outcome was safety and tolerability, with secondary objectives assessing vaccine-specific immunogenicity. The primary immunological outcome was a four times increase (seroconversion) from baseline in spike-specific or nucleocapsid-specific IgG titres within 28 days of the last injection, and seroconversion rates were compared with participants who received placebo using Fisher's exact test. Additional secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ClinicalTrials.gov, NCT046339466. FINDINGS: Between Dec 13, 2020, and May 24, 2021, 56 participants initiated vaccination. On day 0 and 28, 17 participants received low-dose COH04S1, eight received medium-dose COH04S1, nine received high-dose COH04S1, five received placebo, 13 received low-dose COH04S1 followed by placebo, and four discontinued early. Grade 3 fever was observed in one participant who received low-dose COH04S1 and placebo, and grade 2 anxiety or fatigue was seen in one participant who received medium-dose COH04S1. No severe adverse events were reported. Seroconversion was observed in all 34 participants for spike protein and 32 (94%) for nucleocapsid protein (p<0·0001 vs placebo for each comparison). Four times or more increase in SARS-CoV-2 neutralising antibodies within 56 days was measured in nine of 17 participants in the low-dose COH04S1 group, all eight participants in the medium-dose COH04S1 group, and eight of nine participants in the high-dose COH04S1 group (p=0·0035 combined dose levels vs placebo). Post-prime and post-boost four times increase in spike-specific or nucleocapsid-specific T cells secreting interferon-γ was measured in 48 (98%; 95% CI 89–100) of 49 participants who received at least one dose of COH04S1 and provided a sample for immunological analysis. INTERPRETATION: COH04S1 was well tolerated and induced spike-specific and nucleocapsid-specific antibody and T-cell responses. Future evaluation of this COVID-19 vaccine candidate as a primary or boost vaccination is warranted. FUNDING: The Carol Moss Foundation and City of Hope Integrated Drug Development Venture programme. The Author(s). Published by Elsevier Ltd. 2022-04 2022-03-09 /pmc/articles/PMC8906816/ /pubmed/35287430 http://dx.doi.org/10.1016/S2666-5247(22)00027-1 Text en © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license 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 Articles
Chiuppesi, Flavia
Zaia, John A
Frankel, Paul H
Stan, Rodica
Drake, Jennifer
Williams, Brenda
Acosta, Anne Marie
Francis, Karyn
Taplitz, Randy A
Dickter, Janet K
Dadwal, Sanjeet
Puing, Alfredo G
Nanayakkara, Deepa D
Ash, Patricia
Cui, Yujie
Contreras, Heidi
La Rosa, Corinna
Tiemann, Katrin
Park, Yoonsuh
Medina, Joybelle
Iniguez, Angelina
Zhou, Qiao
Karpinski, Veronica
Johnson, Daisy
Faircloth, Katelyn
Kaltcheva, Teadora
Nguyen, Jenny
Kha, Mindy
Nguyen, Vu H
Francisco, Sandra Ortega
Grifoni, Alba
Wong, Angela
Sette, Alessandro
Wussow, Felix
Diamond, Don J
Safety and immunogenicity of a synthetic multiantigen modified vaccinia virus Ankara-based COVID-19 vaccine (COH04S1): an open-label and randomised, phase 1 trial
title Safety and immunogenicity of a synthetic multiantigen modified vaccinia virus Ankara-based COVID-19 vaccine (COH04S1): an open-label and randomised, phase 1 trial
title_full Safety and immunogenicity of a synthetic multiantigen modified vaccinia virus Ankara-based COVID-19 vaccine (COH04S1): an open-label and randomised, phase 1 trial
title_fullStr Safety and immunogenicity of a synthetic multiantigen modified vaccinia virus Ankara-based COVID-19 vaccine (COH04S1): an open-label and randomised, phase 1 trial
title_full_unstemmed Safety and immunogenicity of a synthetic multiantigen modified vaccinia virus Ankara-based COVID-19 vaccine (COH04S1): an open-label and randomised, phase 1 trial
title_short Safety and immunogenicity of a synthetic multiantigen modified vaccinia virus Ankara-based COVID-19 vaccine (COH04S1): an open-label and randomised, phase 1 trial
title_sort safety and immunogenicity of a synthetic multiantigen modified vaccinia virus ankara-based covid-19 vaccine (coh04s1): an open-label and randomised, phase 1 trial
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906816/
https://www.ncbi.nlm.nih.gov/pubmed/35287430
http://dx.doi.org/10.1016/S2666-5247(22)00027-1
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