An in depth investigation of the safety and immunogenicity of an inactivated SARS CoV 2 vaccine

BACKGROUND In-depth investigations of the safety and immunogenicity of inactivated SARS-CoV-2 vaccines are needed. METHOD In a phase I randomized, double-blinded, and placebo-controlled trial involving 192 healthy adults 18-59 years of age, two injections of three different doses (50 EU, 100 EU and 150 EU) of an inactivated SARS-CoV-2 vaccine or the placebo were administered intramuscularly with a 2- or 4-week interval between the injections. The safety and immunogenicity of the vaccine were evaluated within 28 days. FINDING In this study, 191 subjects assigned to three doses groups or the placebo group completed the 28-day trial. There were 44 adverse reactions within the 28 days, most commonly mild pain and redness at the injection site or slight fatigue, and no abnormal variations were observed in 48 cytokines in the serum samples of immunized subjects. The serum samples diluted from 1:32 to 1:4096 and incubated with the virus did not show antibody-dependent enhancement effects (ADEs) with regard to human natural killer cells, macrophages or dendritic cells. At day 14, the seroconversion rates had reached 92%, 100% and 96% with geometric mean titers (GMTs) of 18.0, 54.5 and 37.1, and at day 28, the seroconversion rates had reached 80%, 96% and 92% with GMTs of 10.6, 15.4 and 19.6in 0, 14 and 0, 28 procedures, respectively. Seroconversion was associated with the synchronous upregulation of ELISA antibodies against the S protein, N protein and virion and a cytotoxic T lymphocyte (CTL) response. Transcriptome analysis shaped the genetic diversity of immune response induced by the vaccine. INTERPRETATION In a population aged 18-59 years, this inactivated SARS-CoV-2 vaccine was safe and immunogenic. Trial registration NCT04412538 FUNDING The National Key R&D Program of China (2020YFC0849700), the Program of Chinese Academy of Medicine Science and the Major Science and Technology Special Projects of Yunnan Province. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT04412538 ### Funding Statement This work was supported by National Key R&D Program of China (2020YFC0849700), the Program of Chinese Academy of Medicine Science and the Major science and technology special projects of Yunnan Province. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was reviewed and approved by the Ethics Committee of the West China Second University Hospital, Sichuan University. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data were available.The raw microarray data were submitted to the National Genomics Data Center (NGDC) and are available (PRJCA003531).