Genexine’s Covid-19 DNA vaccine candidate GX-19N showed both potential and limitation, according to the results of a phase-1 trial released on Wednesday.

The company published the results in medRxiv, an open website for medical journals.

Genexine conducted the phase-1 trial to evaluate the safety and immunogenicity of GX-19N in 21 healthy adults aged between 19 and 55. Trial participants received two injections of GX-19N 3mg four weeks apart.

The results showed that 81 percent of the study participants had at least a four-fold increase in spike protein and receptor-binding domain (RBD) antigen-specific binding antibody levels. Also, neutralizing antibodies significantly increased after the administration of GX-19N, the company said.

However, geometric mean titers (GMT) of neutralizing antibodies in vaccinated people with GN-19N fell rapidly over time even after receiving the second shot.

On day 57, GMT in the vaccination group was 37.26, lower than those from human convalescent serum (288.78). This means that the duration of GX-19N DNA’s antigen binding antibody responses was too short.

“Neutralizing antibody levels fell too low in just two months, despite the second shot of the vaccine candidate,” said a specialist physician after reviewing the phase-1 trial data. “The levels are too low that the company may have to reconsider the effectiveness of the vaccine candidate.”

Genexine acknowledged the efficacy issue.

“In the pseudotype virus neutralization assay (PsVNA), neutralizing antibodies were formed in all participants, but such effect did not show in the real Covid-19 virus test,” an official at Genexine said. “It means that we have more challenges to tackle in the next trials.”

The company plans to prove the vaccine’s efficacy either in the current trial or the next.

Genexine said it would continue to develop GX-19N because it proved safety and potential as a treatment for virus variants.

The company emphasized that the phase-1 study confirmed the excellent safety of GX-19N.

When verifying a DNA vaccine’s safety, however, researchers should check whether the modulation of cellular immunity or humoral immunity of the immune system causes unintended adverse reactions such as immunosuppression, chronic inflammatory response, and autoimmune response.

The phase-1 study outcomes showed that 12 participants (57.1 percent) had treatment-emergent adverse events (TEAEs) after receiving GX-19N 3mg.

Among them, five (23.8 percent) had solicited local AEs, and two (9.5 percent) solicited systemic AEs. Most AEs disappeared within three days.

The 12 participants had 10 grade 1 adverse drug reactions (ADR) suspected of a causal relationship with the vaccine. However, no participant had serious adverse reactions or discontinued the trial due to side effects, Genexine said.

The company used an electroporator to deliver the vaccines.

Unlike mRNA vaccines that could cause serious adverse reactions due to the use of additional substances with lipid nanoparticles (LNP), a DNA vaccine poses much less risk because an electroporator injects DNA only, an official at Genexine said.

The company is pinning high hopes on the T-cell immune response data.

The phase-1 data showed that 18 out of 20 trial participants showed spike- and nucleocapsid protein-specific T-cell responses similar to or better than those in convalescent Covid-19 patients, Genexine said.

The company also examined whether the nucleocapsid protein-specific T cell responses induced by GX-19N were also specific to that of Covid-19 virus variants, such as B.1.1.7 (the U.K.), N.1.351 (South Africa), and P.1 (Brazil).

It found that the amino acid sequences identified by T-cell in GX-19N-vaccinated participants were identical with those of Covid-19 variants.

“These results imply that the nucleocapsid protein-specific T cell responses induced by GX-19N can be cross-reactive with emerging Covid-19 virus variants,” the company said.