Exploring the safety and immunogenicity of KD-414, a novel SARS-CoV-2 vaccine

Exploring the safety and immunogenicity of KD-414, a novel SARS-CoV-2 vaccine

In a recent study published in medRxiv * On the preprint server, researchers evaluated the immunogenicity and safety of KD-414, an inactivated vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Studie: Vorläufiger Bericht: Sicherheit und Immunogenität eines inaktivierten SARS-CoV-2-Impfstoffs, KD-414, bei gesunden erwachsenen Teilnehmern: eine nicht randomisierte, offene klinische Phase-2/3-Studie in Japan. Bildquelle: ktsdesign/Shutterstock

*Important NOTE:medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, intended to guide clinical practice/health-related behavior, or treated as established information.

background

The inactivated, purified whole-virus SARS-CoV-2 vaccine is a modality proven to be a safe and effective vaccine against infectious diseases and is used in the KD-414 vaccine. In Phase 1/2 studies, the safety and immunogenicity of the vaccine were evaluated after two intramuscular injections of KD-414 at three different doses containing different active ingredients. These doses included Product L at 2.5 g/dose, Product M at 5 g/dose, and Product H at 10 g/dose.

Although it has been demonstrated that the concentration of neutralizing antibodies strongly corresponds to the preventive effect of the novel SARS-CoV-2 vaccine against the outbreak, the minimum level of neutralizing antibody titers required for prevention has not yet been found. Therefore, it is crucial to evaluate the vaccination schedule based on the first three doses of primary vaccination, which can increase neutralizing antibody titers.

About the study

In the present study, investigators reported the results of Phase 2/3 research conducted to determine the immunogenicity and safety of three doses of KD-414 against SARS-CoV-2.

The team conducted a multicenter, uncontrolled study at 12 sites in Japan. Healthy Japanese volunteers who were at least 18 years old were eligible to take part in the study. Participants who reported fever, cough, chills, shortness of breath or shortness of breath for at least 24 hours or who experienced arthralgia, dysgeusia, diarrhea, headache, myalgia, malaise, nausea, runny nose, olfactory impairment, sore throat, nasal congestion or vomiting for at least 48 hours were instructed to undergo laboratory tests including polymerase chain reaction (PCR).

The active ingredients were administered in an amount of 10 g/dose of KD-414. Three vaccines were provided for primary vaccination: two intramuscular KD-414 doses 28 days apart and one intramuscular vaccination 13 weeks after the second vaccination. Participants who agreed to the third vaccination received the third dose. In an electronic diary, each participant tracked their health status and body temperature from the day after each KD-414 vaccination until day six. A follow-up examination was carried out on the test subjects 28 days after the third vaccination.

The primary endpoint against the Wuhan strain SARS-CoV-2 was the geometric mean neutralizing antibody titers (GMTs) corresponding to KD-414 28 days after the second and third vaccinations. The secondary endpoint was neutralizing antibody seroconversion rates 28 days after the second and third doses of KD-414.

Results

A total of 2,500 participants were vaccinated with the first dose of KD-414, while 2,474 participants received the second dose and 2,081 people were vaccinated with the third dose. 243 participants continued the follow-up phase after receiving the second dose of vaccination because they did not consent to the third vaccination. In addition, of the 295 participants who underwent immunogenicity analysis, 291 were vaccinated with the second dose, while 291 were immunized with the third dose.

None of the participants died after vaccination. Four subjects experienced four serious adverse events (SAEs), excluding death, between the first dose of the KD-414 vaccine and 28 days after the second vaccination, and between the third vaccination and 28 days after the third vaccination.

The GMTs corresponding to the SARS-CoV-2 pseudovirus were 139.6 and 285.6 28 days after the second and third KD-414 vaccinations, respectively. This suggested an increase of almost double after the third vaccination compared to that after the second dose. The rates of seroconversion of neutralizing antibodies were 67.0% and 84.5% after vaccination with the second and third doses, respectively. For the age groups 18 to 40 years, 41 to 64 years and 65 years and older, the neutralization GMTs 28 days after the second vaccination were 199.9, 103.2 and 50.7 and 28 days after the third vaccination were 327.6, 272.2. or 128.0.

Overall, the study results supported the advancement of KD-414 in subsequent phases of clinical trials. In particular, the 18- to 40-year-old age group showed high neutralizing antibody titers after three-dose therapy with KD-414.

*Important NOTE:medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, intended to guide clinical practice/health-related behavior, or treated as established information.

Reference:

• Vorläufiger wissenschaftlicher Bericht.
  Keishi Kido, Kayo Ibaragi, Mitsuyoshi Tanishima, Yosuke Muramoto, Shun Nakayama, Kohei Ata, Kenshi Hayashida, Hideki Nakamura, Yasuhiko Shinmura, Yoshiaki Oda, Masafumi Endo, Kengo Sonoda, Yuji Sasagawa, Yasuhiro Iwama, Kohji Ueda, Takayuki Matsumoto. (2022). Vorläufiger Bericht: Sicherheit und Immunogenität eines inaktivierten SARS-CoV-2-Impfstoffs, KD-414, bei gesunden erwachsenen Teilnehmern: eine nicht randomisierte, offene klinische Phase-2/3-Studie in Japan. medRxiv. doi: https://doi.org/10.1101/2022.10.27.22281603 https://www.medrxiv.org/content/10.1101/2022.10.27.22281603v1