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

Flavia Chiuppesi, PhD; John A Zaia, ProfMD; Paul H Frankel, ProfPhD; Rodica Stan, PhD; Jennifer Drake, RN; Brenda Williams, RN; Anne Marie Acosta, LVN; Karyn Francis, RN; Randy A Taplitz, ProfMD; Janet K Dickter, MD; Sanjeet Dadwal, MD; Alfredo G Puing, MD; Deepa D Nanayakkara, MD; Patricia Ash, RN; Yujie Cui, MS; Heidi Contreras, PhD; Corinna La Rosa, PhD; Katrin Tiemann, PhD; Yoonsuh Park, PhD; Joybelle Medina, MS; Angelina Iniguez, MS; Qiao Zhou, MS; Veronica Karpinski, MS; Daisy Johnson, MS; Katelyn Faircloth, MS; Teadora Kaltcheva, PhD; Jenny Nguyen, MS; Mindy Kha, MS; Vu H Nguyen, PhD; Sandra Ortega Francisco, PhD; Alba Grifoni, PhD; Angela Wong, MS; Alessandro Sette, PhD; Felix Wussow, PhD; Don J Diamond, ProfPhD

The Lancet Microbe (Apr 2022)

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

Flavia Chiuppesi, PhD,
John A Zaia, ProfMD,
Paul H Frankel, ProfPhD,
Rodica Stan, PhD,
Jennifer Drake, RN,
Brenda Williams, RN,
Anne Marie Acosta, LVN,
Karyn Francis, RN,
Randy A Taplitz, ProfMD,
Janet K Dickter, MD,
Sanjeet Dadwal, MD,
Alfredo G Puing, MD,
Deepa D Nanayakkara, MD,
Patricia Ash, RN,
Yujie Cui, MS,
Heidi Contreras, PhD,
Corinna La Rosa, PhD,
Katrin Tiemann, PhD,
Yoonsuh Park, PhD,
Joybelle Medina, MS,
Angelina Iniguez, MS,
Qiao Zhou, MS,
Veronica Karpinski, MS,
Daisy Johnson, MS,
Katelyn Faircloth, MS,
Teadora Kaltcheva, PhD,
Jenny Nguyen, MS,
Mindy Kha, MS,
Vu H Nguyen, PhD,
Sandra Ortega Francisco, PhD,
Alba Grifoni, PhD,
Angela Wong, MS,
Alessandro Sette, PhD,
Felix Wussow, PhD,
Don J Diamond, ProfPhD

Affiliations

Flavia Chiuppesi, PhD: Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA, USA
John A Zaia, ProfMD: Center for Gene Therapy, City of Hope National Medical Center, Duarte, CA, USA
Paul H Frankel, ProfPhD: Department of Biostatistics, City of Hope National Medical Center, Duarte, CA, USA
Rodica Stan, PhD: Translational Development Center, City of Hope National Medical Center, Duarte, CA, USA
Jennifer Drake, RN: Clinical Trials Office, City of Hope National Medical Center, Duarte, CA, USA
Brenda Williams, RN: Clinical Trials Office, City of Hope National Medical Center, Duarte, CA, USA
Anne Marie Acosta, LVN: Clinical Trials Office, City of Hope National Medical Center, Duarte, CA, USA
Karyn Francis, RN: Clinical Trials Office, City of Hope National Medical Center, Duarte, CA, USA
Randy A Taplitz, ProfMD: Division of Infectious Diseases, City of Hope National Medical Center, Duarte, CA, USA; Department of Medicine, City of Hope National Medical Center, Duarte, CA, USA
Janet K Dickter, MD: Division of Infectious Diseases, City of Hope National Medical Center, Duarte, CA, USA; Department of Medicine, City of Hope National Medical Center, Duarte, CA, USA
Sanjeet Dadwal, MD: Division of Infectious Diseases, City of Hope National Medical Center, Duarte, CA, USA; Department of Medicine, City of Hope National Medical Center, Duarte, CA, USA
Alfredo G Puing, MD: Division of Infectious Diseases, City of Hope National Medical Center, Duarte, CA, USA; Department of Medicine, City of Hope National Medical Center, Duarte, CA, USA
Deepa D Nanayakkara, MD: Division of Infectious Diseases, City of Hope National Medical Center, Duarte, CA, USA; Department of Medicine, City of Hope National Medical Center, Duarte, CA, USA
Patricia Ash, RN: Clinical Trials Office, City of Hope National Medical Center, Duarte, CA, USA; Department of Medicine, City of Hope National Medical Center, Duarte, CA, USA
Yujie Cui, MS: Department of Biostatistics, City of Hope National Medical Center, Duarte, CA, USA
Heidi Contreras, PhD: Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Corinna La Rosa, PhD: Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Katrin Tiemann, PhD: Translational Development Center, City of Hope National Medical Center, Duarte, CA, USA
Yoonsuh Park, PhD: Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Joybelle Medina, MS: Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Angelina Iniguez, MS: Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Qiao Zhou, MS: Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Veronica Karpinski, MS: Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Daisy Johnson, MS: Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Katelyn Faircloth, MS: Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Teadora Kaltcheva, PhD: Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Jenny Nguyen, MS: Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Mindy Kha, MS: Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Vu H Nguyen, PhD: Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Sandra Ortega Francisco, PhD: Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Alba Grifoni, PhD: Division of Vaccine Discovery, La Jolla Institute for Immunology and University of California San Diego, La Jolla, CA, USA
Angela Wong, MS: Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Alessandro Sette, PhD: Division of Vaccine Discovery, La Jolla Institute for Immunology and University of California San Diego, La Jolla, CA, USA
Felix Wussow, PhD: Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Don J Diamond, ProfPhD: Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA, USA; Correspondence to: Prof Don J Diamond, Department of Hematology and Hematopoietic Cell Transplantation and Hematologic Malignancies Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA

Journal volume & issue: Vol. 3, no. 4
pp. e252 – e264

Abstract

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Summary: 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/m2 or less, and no modified vaccinia virus Ankara or poxvirus vaccine in the past 12 months. In the open-label cohort, 1·0 × 107 plaque-forming units (PFU; low dose), 1·0 × 108 PFU (medium dose), and 2·5 × 108 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.

Published in The Lancet Microbe

ISSN: 2666-5247 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Medicine (General); Science: Microbiology
Website: https://www.journals.elsevier.com/the-lancet-microbe

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