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 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

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

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.

Informations de copyright

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Déclaration de conflit d'intérêts

DJD and FW are co-inventors on a patent application covering the design and construction of the synthetic modified vaccinia Ankara platform (PCT/US2021/016247). DJD, FW, and FC are co-inventors on a patent application covering the development of a COVID-19 vaccine (PCT/US2021/032821). FC, JAZ, PHF, RS, JD, BW, AMA, KFr, RAT, JKD, SD, AGP, DDN, PA, YC, HC, CLR, KT, YP, JM, AI, QZ, VK, DJ, KFa, TK, JN, MK, VHN, SOF, AW, FW, and DJD are employees of City of Hope National Medical Center (Duarte, CA, USA), which developed the vaccine and funded the trial. AS is a consultant for Gritstone, Flow Pharma, Merck, Epitogenesis, Gilead, and Avalia. La Jolla Institute for Immunology has filed for patent protection for various aspects of T-cell epitope and vaccine design work. All other authors declare no competing interests.