Randomized Controlled Trial
Study population and setting
This is a phase I randomized, double blinded, placebo-controlled trial of inactivated SARS-CoV-2 vaccine in adults aged between 18-59 years. The study included 191 healthy individuals divided into 8 groups, 24 participants each except for one group that had only 23 participants. Although the ethnicity of the participants was not mentioned, the study was conducted in China and presumably all the participants were Chinese. The participants were randomized into 2 broad groups: one group received the vaccination at days 0 and 14, while the other group received the vaccine at days 0 and 28. Each group was further divided into four subgroups that received either one of three different doses (50, 100, 150 EU) of the vaccine or a placebo. In addition to the safety of the vaccine, immunogenicity was also assessed by measuring the development of antibodies against different viral antigens and the expression and cytokine profiles in immune cells.
Summary of Main Findings
The study found the vaccine is generally safe with no severe adverse reactions detected in any of the participants for 28 days after the last vaccine inoculation. Mild reactions were seen in up to 33% of participants at the site of injection (pain, itching, redness and swelling) and systemic (fatigue, diarrhea, fever and rash). The vaccine did not cause an increase in the entry of the virus into immune cells, a phenomenon called antibody-dependent enhancement. Generally, the groups that received the vaccine at 0 and 14 days developed higher levels of neutralizing antibodies relative to the groups who received their vaccination at days 0 and 28. The expression profile of immune cells also showed upregulation of T cells, B cells and antigen presenting cells, suggesting their activation.
While most of the vaccines focus on SARS-CoV-2 spike protein that binds to ACE2 receptor, the vaccine tested in this study uses a different strategy. The study tested inactivated whole virion and showed that it induces antibodies against different viral antigens. Another strength is the concurrent testing of 2 different vaccination protocols (2 vaccine doses at 2 week and 4 week intervals) and three different doses. Finally, while the main purpose of phase I studies is to assess the safety, the study also investigated the immunogenicity of the vaccine.
Most of the limitations are related to the nature of phase I trials, mainly due to the small number of participants. The study also did not include participants from COVID-19 high risk groups (older than 60 years or with diseases affecting the immune system). The assessment of cellular immune response was done indirectly by expression and cytokine profiles rather than directly testing the response of the immune cells to the viral antigens.
This study tested a new strategy for SARS-CoV-2 vaccine using the whole inactivated virion instead of viral spike protein that most other vaccines are targeting.
This review was posted on: 10 November 2020