**12. CoronaVac (Sinovac life sciences, Beijing, China)**

CoronaVac (Sinovac Life Sciences, Beijing, China) represents one of the inactivated vaccine platform and revealed high immunogenic effects in the preclinical studies in mice, rats, and nonhuman primates. The generated antibodies produced from the immunization of CoronaVac have the ability to neutralize several SARS-CoV-2 variants. Following a SARS-CoV-2 challenge in macaques, the data showed that CoronaVac conferred partial or complete protection and prevent the severe interstitial pneumonia with no detectable antibody-dependent increase of infection, supporting the advance to human clinical trials [57].

The SARS-CoV-2 (CN02 strain) has been transfected into the vero cells and then the virus was collected, treated with β-propiolactone. Then the virus was purified, and absorbed onto aluminum hydroxide. The aluminum hydroxide is used as an adjuvant to induce cellular immunity. The vaccine used in the phase 1 study was prepared using cell factory technology, while the vaccine used in phase2 was prepared by using a highly automated bioreactor. The results showed that the CoronaVac (Sinovac) produced for the phase 2 clinical trial has been enhanced the immunogenic results. Vaccine doses of 3 and 6 μg were injected intramuscularly on either day 0 and day 14 or day 0 and day 28, depending on the cohort. Two doses (days 0 and 28) of 6 μg vaccine

yielded the largest antibody recovery, but 3 μg was selected for phase 3 studies based on production capacity (seroconversion rates of 100 and 97%, respectively) [58].

Concerns have been raised about the level of the generated antibodies. The geometric mean titer (GMT) of neutralizing S-IgG was lower than that of convalescent human serum (HCS) while the antibodies arising from natural infection was (mean GMT23.8-65.4). Meanwhile, the results of other vaccine candidates showed that GMT S IgG was superior to HCS. The low immunogenicity of CoronaVac's is represented as one of the obstacles that face this vaccine. The low immunogenic effect of CoronaVac's is may be due to the alteration of S protein induced by the chemical compounds. These vaccine doses were proven to confer the protection against SARS-CoV-2 infection in macaques. CoronaVac is proved to be tolerated and able to generate humoral responses against COVID-19. These findings are paving the way for its emergency use in China and on phase 3 clinical trials. The therapeutic value of CoronaVac remains to be evaluated.
