Interim results of phase-1-2 trials find inactivated coronavirus vaccine is safe

Flu vaccine

Interim results of Phase-1 and Phase-2 trials of an inactivated SARS-CoV-2 vaccine carried out in China show that the vaccine is well tolerated, safe, and produced neutralizing antibodies at 14 days after booster vaccination. Over 90% receiving the vaccine developed neutralizing antibodies.

Interim results of Phase-1 and Phase-2 trials of an inactivated SARS-CoV-2 vaccine carried out in China show that the vaccine is well tolerated, safe, and produced neutralizing antibodies at 14 days after booster vaccination. Over 90% receiving the vaccine developed neutralizing antibodies. “Most participants started to generate antibody responses after the second injection, and remained at high levels 14 days after the third injection.”

The most common adverse reaction seen was pain at the injection site, followed by fever, which were mild and self-limiting. No serious adverse reactions were noted, the researchers write in a paper published in the Journal of the American Medical Association.  No antibody-dependent enhancement (ADE) phenomenon was observed.

The interim analysis was carried based on data up to 14 days after two injections in both phases, and also data from three different doses and three injection procedures in the case of Phase-1 and two injections procedures in the case of Phase-2 trial.

The vaccine candidate tested by China — inactivated viruses with an alum adjuvant —  is similar to the vaccine (Covaxin) candidate design now being tested by the Hyderbad-based Bharat Biotech. While one of the vaccines tested by Bharat Biotech contains only alum adjuvant, the second coronavirus vaccine that is tested contains alum plus another compound as an adjuvant. Hence, the safety of the vaccine and its ability to elicit neutralising antibodies offers hope that Bharat Biotech’s vaccine too may behave similarly.

Antibody responses

The neutralizing antibody response was monitored over 14 days after injections. Data suggest that the “inactivated vaccine may effectively induce antibody production”. “The antibody titers started to increase after the second injection and further increased after the third injection, suggesting the need for a booster injection,” they write.

The magnitude of the antibody responses was not compared with convalescent serum samples but was compared with published results from other COVID-19 vaccine trials. The neutralizing antibody titers were “comparable with the levels” in other studies using a similar method such Moderna and Oxford vaccine and “higher” than adenovirus-vector vaccine, they write.

The trials were designed by the Wuhan Institute of Biological Products Co Ltd and Henan Provincial Center for Disease Control and Prevention (CDC) and conducted in Henan Province, China. Phase-1 trial involved 96 participants, while the Phase-2 trial was among 224 participants. The participants were in the age group 18-59 years. The enrollment began on April 12 and the interim analysis was conducted on June 16.

Design of trials

For the Phase-1 trial, three different doses (2.5 microgram, 5 microgram, and 10 microgram) were tested on 24 participants each. Each participant received three doses of the vaccine on days 0, 28, and 56. The control arm received only the alum adjuvant.

Participants were randomly assigned to either receive one of the three vaccine doses or a placebo (alum adjuvant in this case). Neither the participants nor the principal investigators knew who was receiving the vaccine and who was not, which is called a double-blind study.

For the Phase-2 trial, only one dose (5 microgram) was tested on 224 healthy participants. Each participant received two doses of the vaccine either on days 0 and 14 or on days 0 and 21. Each arm had 84 participants. The control arm with 28 participants received only the alum adjuvant. Participants were randomly assigned to either receive the vaccine or a placebo (alum adjuvant in this case). It was a double-blind study.

Participants receiving three different doses did not get the candidate vaccine at the same time. Instead, in Phase-1 trial, those belonging to the low-dose received injections first, and adverse events were monitored for seven days. Participants in the medium-dose group received the candidate vaccine only on day eight when no serious adverse events were seen in those who received the low-dose. Similar procedure was followed for the high-dose vaccination.

Even in the case of Phase-2, participants received the medium dose only on day eight after participants in Phase-1 received the medium dose and when no serious adverse events were reported.