CHENGDU, China—Clover Biopharmaceuticals, a clinical-stage biotechnology company, announced recently that it has successfully produced its trimeric Spike-protein (S-Trimer) subunit vaccine candidate for 2019-nCoV (the novel coronavirus that seems to have started in Wuhan, China) via a mammalian cell expression system. In addition, Clover scientists have used the newly obtained S-Trimer and successfully detected antigen-specific antibody in sera from multiple fully recovered patients who were previously infected by the virus.
Importantly, Clover asserts, it is the first company in the world to disclose a 2019-nCoV vaccine candidate that can successfully be recognized by antibodies produced by previously infected patients, supporting that S-Trimer has preserved the native structure of the viral spike (S) protein and thus may elicit a protective-immune response as a vaccine. This work was carried out with the support of leadership teams from Chengdu Hi-Tech Park and Chengdu Clinical Center for Public Health in China.
Similar to other enveloped RNA viruses such as HIV, RSV and influenza, 2019-nCoV is also an RNA virus that has a trimeric spike (S) protein on its viral envelope. The trimeric S protein of 2019-nCoV is responsible for binding to host cell surface receptor ACE2 and subsequent viral entry. Symptoms in infected patients include fever, coughing and breathing difficulties, and it can be fatal.
Upon determining the genomic DNA sequence of 2019-nCoV last month, Clover scientists immediately started designing the viral S-protein construct and completed its gene synthesis. Utilizing its patented Trimer-Tag technology, Clover produced a S-Trimer subunit vaccine that resembles the native trimeric viral spike via a rapid mammalian cell-culture based expression system. The company says it has one of the largest in-house, commercial-scale cGMP biomanufacturing capabilities in China, which therefore could potentially be able to rapidly scale up and produce large quantities of a coronavirus vaccine.
Clover notes that it has previously developed recombinant subunit-Trimer vaccines for RSV and influenza viruses utilizing its Trimer-Tag technology, and has demonstrated that such vaccines are capable of triggering protective neutralizing antibody responses in multiple animal models.
“The implication of this discovery is that it not only has validated the correct conformation of our S-Trimer subunit vaccine candidate, but also further supports that the new 2019-nCov virus is indeed the culprit for the current epidemic, since all previous diagnosis for the viral infections have been based on nucleic acid detection,” said Dr. Peng Liang, co-founder, chairman and president of Clover. “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. We remain confident that Clover can be among one of the first companies to develop a successful vaccine to contain the 2019-nCoV epidemic, as well as any future outbreaks of similar coronaviruses.”
Added Joshua Liang, chief strategy officer and board director at Clover: “We are encouraged by the rapid progress of our S-Trimer vaccine development for 2019-nCoV and hope to support global efforts in fighting this epidemic. To this end, we recognize that collaborations will be critical to accelerating the development of a successful new vaccine in times of emergency, and we invite any interested regulatory, academic or industry parties to contact us for this noble common cause.”
Clover is, of course, not the only entity hurrying to find vaccines or other therapeutics against the new virus. For example, Cambridge, Mass.-based Moderna Inc. and the Coalition for Epidemic Preparedness Innovations (CEPI), recently announced a new collaboration to develop an mRNA vaccine against 2019-nCoV. Under the terms of the agreement, Moderna will manufacture an mRNA vaccine against 2019-nCoV, which will be funded by CEPI. The Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), collaborated with Moderna to design the vaccine. NIAID will conduct IND-enabling studies and a Phase 1 clinical study in the United States.
Over the past four years, Moderna has had six positive Phase 1 clinical readouts in its prophylactic vaccines modality and moved two additional programs into development. Moderna’s technology platform, fully integrated manufacturing site and development experience—combined with a multi-year relationship with the NIH, including exploring ways to respond to public health threats—allows for the rapid identification and advancement of a vaccine candidate against 2019-nCoV.
Gilead Sciences Inc. is also in the race, having recently started providing doses of remdesivir (GS-5734), which was initially developed to combat Ebola crisis, for the emergency treatment of “a small number of patients” who have contracted the new coronavirus. The company is also working with health authorities in China to start a Phase 3 clinical trial to determine if the drug can fight this new viral strain.
Noted Gilead: “While there are no antiviral data for remdesivir that show activity against 2019-nCoV at this time, available data in other coronaviruses give us hope. Remdesivir has demonstrated in-vitro and in-vivo activity in animal models against the viral pathogens MERS and SARS, which are coronaviruses that are structurally similar to 2019-nCoV. There are also limited clinical data available from the emergency use of remdesivir in the treatment of patients with Ebola virus infection.”