Discussion
®, COVID-19 disease
ADVERSE EVENTS, DISEASE, ADVERSE REACTION, ASYMPTOMATIC COVID-19
We found that the 10-µg FAKHRAVAC inactivated SARS-CoV-2 vaccine elicited significant neutralizing antibody response about six times the placebo group (and nine times to the baseline) four weeks after the second dose. Specific antibodies against S and RBD using the ELIZA method also showed a more than three times increase to the placebo and about six times to the baseline. No suspected unexpected serious adverse reaction (SUSAR) was observed in study participants during the follow-up period of up to 6 months. The three hospitalized COVID-19 cases occurred in the placebo group. All abnormal laboratory findings 1 week after each injection were resolved completely.The follow-up period in our study was 6 months according to the protocol. During this period we collected all medically attended adverse events among study participants and assessed their relationship to the study intervention. However, as COVID-19 vaccines became available for the Iranian general population, it was unethical to deprive the placebo group of the COVID-19 national vaccination programs. Therefore the placebo group in our study were followed for a time period about half the vaccine group.Local and systemic reactogenicity in the first week after the injections were relatively low compared to other inactivated vaccines [We observed a significant neutralizing antibody response in the conventional Virus Neutralization Test (cVNT) two and four weeks after the second dose in the vaccine group compared to the placebo (see Table We showed that FAKHRAVAC elicited a significant immunogenicity response after two doses. Although this does not necessarily translate into the clinical efficacy of the vaccine, there are hints that this may be true. We identified 22 cases of symptomatic PCR-positive COVID-19 disease occurring 2 weeks after the second dose, 8 in the vaccine and 14 in the placebo groups (see Additional file Our study had also some limitations. First, we were unable to continue the follow-up of the placebo group beyond 3 months because approved COVID-19 vaccines became available for the Iranian general population. Second, the number of participants over 50 in our study is relatively low, and the data does not include people over 70, who are an important target population in the vaccination against COVID-19. Third, we did not compare neutralizing antibody titers in our study with that of the convalescent serum samples as positive controls, which could have provided clues to the magnitude of the antibody responses.In summary, we found that the 10-µg/dose FAKHRAVAC® inactivated SARS-CoV-2 vaccine is safe and induces a significant humoral immune response in adults aged 18–70. A future phase III clinical trial is needed to find out if this observed immunogenicity will translate into clinical efficacy in preventing symptomatic COVID-19 disease.