BEIJING – Chinese biotech companies are focusing on fighting the novel coronavirus, now named as COVID-19 by the WHO, after the country’s government called for all possible assistance. With its Trimer-Tag technology, Chengdu-based Sichuan Clover Biopharmaceuticals Inc. is among the first to reveal production of a vaccine candidate against COVID-19.
The trimeric Spike-protein subunit vaccine candidate was produced via a mammalian cell expression system. Clover’s team used the newly obtained trimeric Spike-protein, referred to as S-Trimer, to detect antigen-specific antibody in sera from patients who had recovered from the coronavirus.
“S-Trimer is the first COVID-19 vaccine candidate in the world that can successfully be recognized by cross-reactive antibodies produced by patients previously infected with COVID-19,” Joshua Liang, Clover’s chief strategy officer, told BioWorld.
The company said S-Trimer has preserved the native structure of the viral spike (S) protein and thus may elicit a protective-immune response as a vaccine.
Liang explained that coronavirus is an enveloped RNA virus and, historically, vaccine development for most enveloped RNA viruses has proved challenging due to the structural complexity of trimeric envelope spike proteins. Preserving the native trimeric structure and glycosylation of those viral spike proteins is therefore critical for optimal antigenicity and successful vaccine response.
“We are able to leverage our Trimer-Tag technology to enable the rapid production of secreted, covalently trimerized, native-like subunit vaccines against RNA viruses like coronavirus,” he added.
The patented technology helped Clover produce an S-Trimer subunit vaccine that resembles the native trimeric viral spike via a rapid mammalian cell-culture based expression system.
With the same technology, Clover has previously developed recombinant subunit-Trimer vaccines for respiratory syncytial virus and influenza viruses. Multiple animal models have demonstrated that those vaccines are able to evoke protective neutralizing antibody responses.
The announcement of the development of a vaccine candidate also came earlier than most expected.
“Given that Clover’s R&D team is located in China at the heart of this viral outbreak, we are uniquely positioned to quickly find local collaborators and obtain certain reagents that are important to vaccine development,” Liang told BioWorld. “So, while animal immunization studies are still ongoing for all vaccine candidates around the world, we have been able to rapidly demonstrate this initial proof of concept.”
Clover’s co-founder and chairman, Peng Liang, said being able to use the vaccine candidate to detect viral S protein-specific antibodies from the sera of infected patients is an important move.
He explained that the implication is that it not only has validated the correct conformation of the S-Trimer subunit vaccine candidate, but also further supports the data that the new COVID-19 virus is indeed the culprit for the current epidemic, since all previous diagnoses for the viral infection have been based on nucleic acid detection. “This important finding forms a solid foundation for the continued rapid development of S-Trimer vaccine through pilot production, preclinical efficacy and safety studies, followed by human clinical trials and subsequent large-scale production,” he said.
The Chengdu-based biotech is looking for partners to speed up the development of this vaccine candidate, and it has the manufacturing facilities ready.
“Since we have our own in-house GMP biomanufacturing capabilities, which have up to 2 x 2,000L of bioreactor capacity, we are currently working towards producing a GMP lot to be used for phase I clinical trials, and have the infrastructure to further scale-up production to hundreds of millions of S-Trimer vaccine doses annually if needed,” Joshua Liang told BioWorld.
“We are currently working hard to complete preclinical and nonclinical studies required prior to initiating human studies, with the goal of getting S-Trimer into the clinic within a few months,” he added.
As of Feb 12, the COVID-19 virus has infected more than 44,700 people in China and killed more than 1,000. The outbreak continues to worsen, and public health experts believe the peak has yet to come, as people have just started to return to work in China this week after an extended Chinese New Year holiday.
Currently, there is no vaccine available for the coronavirus. The World Health Organization (WHO) said the first vaccine could be ready in 18 months, with its chief, Tedros Adhanom Ghebreyesus, stating that the public “are not defenseless.”
Biotech companies and researchers in China and abroad have announced plans to develop vaccines against COVID-19.
Beijing Advaccine Biotechnology was said to have raised $4.3 million on Feb. 11 to test a vaccine that it is developing with U.S. firm Inovio Pharmaceutical Inc. Advaccine will conduct the phase I testing in China and plans to complete preclinical development in four to six months.
CRO Wuxi Biologics Cayman Inc. is also stepping up efforts. While it normally takes 15 to 18 months to go from obtaining the DNA of a virus to getting an IND for neutralizing antibodies, Wuxi Biologics CEO Chris Chen told BioWorld previously that the company will “compress the process to four or five months, while complying to all the international standards.”
Moderna Therapeutics Inc. and Johnson & Johnson are among the foreign pharma companies that are dedicating efforts toward the public health threat. Researchers from Hong Kong University, the University of Queensland in Australia and Imperial College London (ICL) have also joined the cause. ICL said its vaccine candidate has entered animal testing.