Safety and immunogenicity of two recombinant DNA COVID-19 vaccines containing the coding regions of the spike or spike and nucleocapsid proteins: an interim analysis of two open-label, non-randomised, phase 1 trials in healthy adults

Abstract

Background We assessed the safety and immunogenicity of two recombinant DNA vaccines for COVID-19: GX-19 containing plasmid DNA encoding the SARS-CoV-2 spike protein, and GX-19N containing plasmid DNA encoding the SARS-CoV-2 receptor-binding domain (RBD) foldon, nucleocapsid protein, and plasmid DNA encoding the spike protein. Methods Two open-label non-randomised phase 1 trials, one of GX-19 and the other of GX-19N were done at two hospitals in South Korea. We enrolled healthy adults aged 19-49 years for the GX-19 trial and healthy adults aged 19-54 years for the GX-19N trial. Participants who tested positive by serological testing for SARS-CoV-2 were excluded. At 4-week intervals, the GX-19 trial participants received two vaccine doses (either 1middot5 mg or 3middot0 mg), and the GX-19N trial participants received two 3middot0 mg doses. The vaccines were delivered intramuscularly using an electroporator. The participants were followed up for 52 weeks after first vaccination. Data collected up to day 57 after first vaccination were analysed in this interim analysis. The primary outcome was safety within 28 days after each vaccination measured in the intention-to-treat population. The secondary outcome was vaccine immunogenicity using blood samples collected on day 43 or 57 after first vaccination measured in the intention-to-treat population. The GX-19 (NCT044445389) and GX-19N (NCT04715997) trials are registered with ClinicalTrials.gov. Findings Between June 17 and July 30, 2020, we screened 97 individuals, of whom 40 (41%) participants were enrolled in the GX-19 trial (20 [50%] in the 1middot5 mg group and 20 [50%] in the 3middot0 mg group). Between Dec 28 and 31, 2020, we screened 23 participants, of whom 21 (91%) participants were enrolled on the GX-19N trial. 32 (52%) of 61 participants reported 80 treatment-emergent adverse events after vaccination. All solicited adverse events were mild except one (2%) case of moderate fatigue in the 1middot5 mg GX-19 group; no serious vaccine-related adverse events were detected. Binding antibody responses increased after second dose of vaccination in all groups (p=0middot0002 in the 1middot5 mg GX-19 group; p<0middot0001 in the 3middot0 mg GX-19; and p=0middot0004 for the spike protein and p=0middot0001 for the RBD in the 3middot0 mg GX-19N group). Interpretation GX-19 and GX-19N are safe and well tolerated. GX-19N induces humoral and broad SARS-CoV-2specific T-cell responses. GX-19N shows lower neutralising antibody responses and needs improvement to enhance immunogenicity. Funding The Korea Drug Development Fund, funded by the Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.