Inactivated novel coronavirus vaccine (PiCoVacc) tested on mice, rats and rhesus macaques was found to be safe, and to provide partial to complete protection in rhesus macaques depending on the dosage (3 microgram or 6 microgram) tested. The Beijing-based Sinovac Biotech’s vaccine was able to induce specific neutralising antibodies in all three animal models. The virus was isolated from 11 hospitalised patients, including intensive care units, from China, Italy, Switzerland, U.K. and Spain.
The vaccine is currently undergoing human clinical trials. In April, the company commenced phase-1 trial on 144 healthy adults aged 18-59 years.
For the animal trial, four different doses of the vaccine mixed with an adjuvant were administered on days zero and seven. The control group was administered a sham vaccine.
Writing in a paper published in the journal Science, Chuan Qin from China’s National Institutes for Food and Drug Control in Beijing and others note that the vaccine was able to quickly induce RBD-specific immunoglobulin G (Ig G) in vaccinated mice. About half of spike protein-induced antibody response came from RBD-specific IgG, suggesting RBD is the dominant immunogen. Incidentally, RBD-specific IgG was found to be the dominant immunogen in the blood of recovered COVID-19 patients. Similar results were seen in Wistar rats too.
Four monkeys were administered either a medium (3 microgram per dose) or high (six microgram per dose) dose of the vaccine on day zero, seven and 14. S-specific IgG and neutralising antibodies were produced during the second week after vaccination in monkeys that received medium and high dose. The titers were similar to those of serum from recovered COVID-19 patients.
On day 21 after the first dose of the vaccine, the monkeys were exposed to coronavirus given through intratracheal route. While the controls had a huge viral load from the day of challenge and even developed severe pneumonia, the vaccinated animals were largely protected. Viral loads decreased significantly in all vaccinated macaques. “All four macaques that received the high dose had no detectable viral loads in pharynx, crissum and lung at day seven after infection,” they write.
The researchers carried out additional safety studies in 10 monkeys divided into two groups. While one group received a low dose (1.5 microgram), the other received a high dose (6 microgram). Compared with the controls, the vaccinated monkeys did not develop fever or weight loss. Blood parameters too remained normal, and histopathological evaluations of various organs, including lung, heart, spleen, liver, kidney and brain did not show any pathology.
“Our data demonstrate complete protection against SARS-CoV-2 challenge with a 6 microgram per dose of PiCoVacc vaccine in macaques. Collectively these results suggest a path forward for clinical development of SARS-CoV-2 vaccines for use in humans,” they write.
