BEIJING – China this week approved both the country’s first mRNA vaccine candidate and its first recombinant protein subunit vaccine to begin clinical trials to fight COVID-19. China National Biotec Group (CNBG)’s vaccine is also entering phase III trials in Beijing, Wuhan and Abu Dhabi, the United Arab Emirates (UAE).
The addition of these two vaccine candidates means China now has seven candidates in its trial pipeline for COVID-19. They include a viral vector-based vaccine and four inactivated vaccines, meaning that the country is adopting four different technologies in the vaccine race.
Known as ARCov, the mRNA vaccine is co-developed by Cansino Biologics Inc. and the Institute of Biotechnology of the Academy of Military Medical Sciences. The IND approval came on June 19, and the phase I trial to evaluate the safety of the candidate will begin at Shulan Hospital in Hangzhou.
Animal studies showed that the mRNA vaccine candidate induced high levels of neutralizing antibodies in mice and cynomolgus monkeys and induced protective T-cell immune responses. The toxicity test on cynomolgus monkeys proved that animals immunized with the vaccine candidate can tolerate attacks from high-titer coronavirus, and that helps in preventing virus replication and the progression of lung pathologies.
“The core raw materials and equipment are all domestically produced to enable rapid manufacture,” said Qin Chengfeng, a researcher responsible for the mRNA project.
He added that the vaccine antigen target selection is more precise, so the induced neutralizing antibody has high specificity and better safety. He also noted that the vaccine comes in a single prefilled injection dosage form, so it can be stored at 4 degrees Celsius for the long term, or at room temperature for a week. The cost for cold chain supply and storage is low, and it is easy to use for mass inoculation.
Just a month ago, Cansino unveiled its collaboration with Canadian company Precision Nanosystems Inc., of Vancouver, British Columbia to develop an mRNA lipid nanoparticle vaccine. Precision will develop the mRNA-LNP vaccine, while Cansino will be responsible for preclinical testing, clinical trials, regulatory approval and commercialization.
“This mRNA vaccine will use a novel lipid delivery technology and the proven microfluidics-based scale-up and manufacturing platform from Precision,” Precision CEO James Taylor told BioWorld.
Cansino CEO Xuefeng Yu said he believes in the mRNA vaccine technology. “RNA vaccines are a disruptive technology as they do not require cell culture, utilize synthetic delivery and have a smaller manufacturing footprint,” he said, adding that this approach can accelerate vaccine development.
Now the world sees three mRNA vaccine candidates in clinical trials. Other biotech companies also known to be adopting that vaccine development technology include Arcturus Therapeutics Inc., Biontech Inc., Pfizer Inc., Sanofi Pasteur, Translate Bio Inc., Stermirna Therapeutics Co. Ltd. and Etherna Immunotherapies NV.
Cansino’s primary vaccine candidate for COVID-19, Ad5-nCoV, is a viral vector-based vaccine that is under a phase II trial. It was the first vaccine to enter clinical trials in China.
Ad5-nCoV was developed with the company’s existing adenovirus-based viral vector vaccine technology platform, which utilizes adenoviruses as viral vectors to deliver vaccine antigens to the human cell.
More trials to start
The Chinese health authority said it expected to see more vaccine candidates entering human trials starting in June.
This week, regulators also granted an IND approval to a recombinant protein subunit vaccine developed by Chongqing Zhifei Biological Products Co. Ltd. and Institute of Microbiology, Chinese Academy of Sciences. The vaccine candidate is developed using CHO cells.
“Animal tests showed that the vaccine candidate can induce high levels of neutralizing antibodies, hence significantly lower viral loads in lungs and reducing lung damage caused by viral infection,” the company said. It added that the vaccine was produced by engineering cell lines, which enables high production volume, low-cost manufacturing and high accessibility.
The first patient was dosed in the phase I study on June 23. According to public information, the phase I trial is a multicenter, double-blind, randomized, placebo parallel controlled study that aims to recruit 50 healthy volunteers, ages 18 to 59 to evaluate the vaccine candidate’s safety and tolerability.
Current vaccine candidates under clinical trials are also making progress. Two are entering phase III trials at home and abroad, placing them amongst the most advanced COVID-19 vaccine candidates.
State-backed CNBG said on June 23 that a phase III trial of its inactivated vaccine will begin in Beijing and Wuhan in China, as well as Abu Dhabi in the UAE. It is working with Group 42 (G42), an AI and cloud computing company in the UAE, to bring the Chinese vaccine to the Middle Eastern country. G42 will conduct the clinical trials under the supervision of the Department of Health Abu Dhabi.
Assuming clinical efficacy, the companies hope the vaccine will enter the market by the end of 2020 or early 2021.
Just a week ago, CNBG said its inactivated COVID-19 vaccine candidate produced a seroconversion rate of up to 100% in a phase I/II trial in volunteers who received two doses 28 days apart. The company added that the vaccine induced high titer antibodies in all inoculated people and demonstrated a favorable safety profile without a single adverse event. More comprehensive data are to be unveiled.
CNBG’s vaccine is being developed by Wuhan Institute of Biological Products, a subsidiary of CNBG, together with the Wuhan Institute of Virology under the Chinese Academy of Science.
Meanwhile, Sinovac Biotech Ltd.’s inactivated vaccine, Coronavac, is also set to enter phase III trials in Brazil in July and is looking to recruit 9,000 volunteers. It is collaborating with the Instituto Butantan to carry out clinical work in the Latin American country.
“We aim to conduct the phase III trial next month,” Pearson Liu, Sinovac’s director of brand management and public relations, told BioWorld. “We plan to conduct the phase III trials in countries that see a high incidence of COVID-19.”
Brazil will also start testing a vaccine candidate this month in a phase III trial developed by researchers at the University of Oxford and Astrazeneca plc, calling on some 2,000 healthy volunteers.
Meanwhile, Moderna has also finalized the protocol for the phase III trial of its vaccine candidate, mRNA-1273. Its trial is expected to start in July and include 30,000 people.