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Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18-59 years: Report of the Randomized, Double-blind, and Placebo-controlled Phase 2 Clinical Trial

Our take —

In this study, available as a preprint and thus not yet peer reviewed, COVID-19 vaccines utilizing inactivated whole SARS-CoV-2 continue to show promise in clinical trial data reported to date, with good safety profiles and acceptable immunogenicity. The vaccine evaluated here – Sinovac’s CoronaVac – likely compares favorably with the virtually identical offering from Sinopharm, although the several limitations noted above hinder more definitive conclusions at this time.Substantial revision will likely be present in any peer-reviewed version of this article, so the evaluation here should be taken with caution. Furthermore, the phase 3 trials currently either planned or underway with this vaccine in Bangladesh, Brazil, and Indonesia should yield crucial additional information.

Study design

Randomized Controlled Trial

Study population and setting

This study reports the findings from a phase 2 clinical trial evaluating the safety and immunogenicity of Sinovac’s CoronaVac COVID-19 vaccine, which consists of β-propiolactone inactivated whole SARS-CoV-2 with an aluminum hydroxide adjuvant. The trial was double-blinded, placebo-controlled, and involved 600 adults (ages 18-59) in Suining County, Jiangsu Province, China. Two doses (3 μg/mL or 6 μg/mL) were utilized in two schedules (injections on days 0 and 14, or days 0 and 28) in a ratio of 2:2:1 between the two vaccinated groups and the placebo group. Safety was assessed by self-reported adverse reactions, and immunogenicity was assessed by measuring total specific IgG against the receptor binding domain (RBD) and by measuring the neutralizing antibody (NAb) response.

Summary of Main Findings

Vaccination with CoronaVac was generally safe, with no serious adverse reactions reported, and immunogenic, with high NAb seroconversion rates (> 90%).

Study Strengths

The study design is generally acceptable and the data indicate that, similarly to the inactivated vaccine in development by Sinopharm, Sinovac’s CoronaVac may have a superior profile to many other vaccine platforms currently in clinical trials.

Limitations

This study has numerous limitations. The safety assessment consisted of only self-reported adverse reactions; blood samples for laboratory analysis were not obtained, and no data were provided regarding some of the specific safety concerns with COVID-19 vaccination (e.g. antibody-dependent enhancement). Immunogenicity was assessed only in terms of humoral response, and the data are not presented clearly (e.g. seroconversion rates are only generically said to be ‘over 90%’). Additionally, the total IgG assay used only the RBD as the antigen, the NAb assay used (a ‘modified cytopathogenic effect’) differs from those employed by most other COVID-19 vaccine studies to date (which use plaque reduction neutralization tests) which makes cross-study comparisons difficult. Also the explanations provided for the improved immunogenicity seen with vaccine formula used in the phase 2 trial versus that used in phase 1 (i.e. a greater amount of spike protein per virion), are questionable and insufficient data are presented for this assessment.

Regarding the phase 1 trial, references to ‘detailed information’ and a ‘coordinated submission’ of the phase 1 results are made, but we are unaware of any information available on the phase 1 results beyond Sinovac press reports and the phase 1 data confusingly scattered throughout this manuscript. Finally, numerous typographical errors (including grammatical/spelling mistakes and formatting irregularities), as well as a generally poor overall structure render this article difficult to read and reduce confidence in the data reported.

Value added

This study is the second to report clinical trial results assessing inactivated SARS-CoV-2 as a vaccine for COVID-19, and lends tentative additional support for this approach.

This review was posted on: 18 September 2020