Safety and immunogenicity of a recombinant DNA COVID-19 vaccine containing the coding regions of the spike and nucleocapsid proteins: Preliminary results from an open-label, phase 1 trial in healthy adults aged 19–55 years

Abstract

Background : We investigated the safety and immunogenicity of two recombinant COVID-19 DNA vaccine candidates in first-in-human trials. GX-19 contains plasmid DNA encoding SARS-CoV-2 spike protein, and GX-19N contains plasmid DNA encoding SARS-CoV-2 receptor binding domain (RBD) foldon and nucleocapsid protein (NP) as well as plasmid DNA encoding SARS-CoV-2 spike protein. Methods : Two open-label phase 1 trials of GX-19 and GX-19N safety and immunogenicity were performed in healthy adults aged 19-55 years. GX-19 trial participants received two vaccine injections (1.5 mg or 3.0 mg, 1:1 ratio) four weeks apart. GX-19N trial participants received two 3.0 mg vaccine injections four weeks apart. Findings : Between June 17 and July 30 and December 28 and 31, 2020, 40 and 21 participants were enrolled in the GX-19 and GX-19N trials, respectively. Thirty-two participants (52.5%) reported 80 treatment-emergent adverse events (AE) after vaccination. All solicited AEs were mild except one case of moderate fatigue reported in the 1.5 mg GX-19 group. Binding antibody responses increased after vaccination in all groups. The geometric mean titers (GMTs) of spike-binding antibodies on day 57 were 85.74, 144.20, and 201.59 in the 1.5 mg, 3.0 mg GX-19 groups and the 3.0 mg GX-19N group, respectively. In GX-19N group, neutralizing antibody response (50% neutralizing titer using FRNT) significantly increased after vaccination, but GMT of neutralizing antibody on day 57 (37.26) was lower than those from human convalescent serum (288.78). GX-19N induced stronger T cell responses than GX-19. The magnitude of GX-19N-induced T cell responses was comparable to those observed in the convalescent PBMCs. GX-19N induced both SARS-CoV-2 spike- and NP-specific T cell responses, and the amino acid sequences of 15-mer peptides containing NP-specific T cell epitopes identified in GX-19N-vaccinated participants were identical with those of diverse SARS-CoV-2 variants Interpretation : GX-19N is safe, tolerated and induces humoral and broad SARS-CoV-2-specific T cell response which may enable cross-reactivity to emerging SARS-CoV-2 variants. Funding : This research was supported by Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (HQ20C0016, Republic of Korea).

The Nucleocapsid Protein of SARS-CoV-2, Combined with ODN-39M, Is a Potential Component for an Intranasal Bivalent Vaccine with Broader Functionality

“…Alternatively, the approach based on conserved antigens could reach a broad scope depending on the level of conservation of the antigen and its proper presentation. The nucleocapsid (N) protein is one example of a conserved antigen that has been tested in different vaccine platforms and combinations with encouraging results against SARS-CoV-2 [ 26 , 27 , 28 , 29 , 30 , 31 ].…”

The Nucleocapsid Protein Of SARS-CoV-2, Combined With ODN-39M, Is A Potential Component For An Intranasal Bivalent Pancorona Vaccine

“…Alternatively, the approach based on conserved antigens could reach a broad scope depending on the level of conservation of the antigen and its proper presentation. The nucleocapsid (N) protein is one example of conserved antigen which has been tested in different vaccine platforms and combinations with encouraging results against SARS-CoV-2 (Chiuppesi et al, 2020) (Ahn et al, 2021) (Thura et al, 2021).…”

COVID-19 mitigation: nanotechnological intervention, perspective, and future scope

“…However, their major drawbacks include the lack of stability and low cellular internalizations under several physiological conditions. Thus, to address this issue, researchers have focused on the development of DNA vaccines and clinical trial runs were carried out under the active guidance of Inovio Pharmaceuticals/International Vaccine Institute, USA, 192 Phase II/III Study of COVID-19 DNA Vaccine (AG0302-COVID19), 193 Study of COVID-19 DNA Vaccine (AG0301-COVID-19), 193 Cadila Healthcare Limited (India), 194 which was predicted to hit the market on June 13 May, 2021, 195 Genexine Consortium (South Korea), 196 Entos Pharmaceuticals Inc. (Canada), 197 GeneOne Life Science, Inc. (South Korea), 198 University of Sydney, Bionet Co., Ltd. Technovalia (Australia), 199 and Takis/Rottapharm Biotech (Italy). 200 Importantly, to bifurcate the insertional mutagenesis, Shim et al and Zhao et al prepared polyethyleneimine and polyethyleneiminestearic acid (PSA) cationic nanomicelles, respectively, for the delivery of mRNA encoding HIV-1 gag to dendritic cells.…”