HONG KONG – Chengdu, China-based Clover Biopharmaceuticals Inc. has teamed up with Emeryville, Calif.-based Dynavax Technologies Corp. on a research collaboration to develop a vaccine candidate to prevent COVID-19.

The partnership will draw on Clover’s protein-based coronavirus vaccine candidate, COVID-19 S-Trimer, which is in the preclinical stage. Dynavax will contribute its Toll-like receptor 9 (TLR9) agonist adjuvant, CpG 1018, and technical expertise to the initiative.

“Dynavax's CpG 1018 adjuvant will be tested with Clover's COVID-19 S-Trimer antigen as a potential vaccine candidate,” Joshua Liang, chief strategy officer for Clover and the co-inventor of its COVID-19 S-Timer, told BioWorld. “Vaccine adjuvants can boost the immune response to the virus antigen. Dynavax's CpG is commercially approved by the FDA use in their hep B vaccine [Heplisav-B] and has a large safety database,”

Clover scientists started working on the viral spike (S)-protein construct and completed its gene synthesis upon learning of the genomic DNA sequence of the newly identified SARS-CoV-2 virus, which causes COVID-19, in late January.

By using its Trimer-Tag technology, the Chinese biotech has produced a COVID-19 S-Trimer subunit vaccine candidate that resembles the native trimeric viral spike via a rapid mammalian cell culture-based expression system.

“SARS-CoV-2 infects host cells via the binding of its spike (S) surface protein to human ACE2 receptors. The S protein naturally forms a trimeric structure on the viral envelope,” said Liang.

He said he believes mimicking its structure on the viral envelope could induce a protective immune response after vaccination.

“We have demonstrated that our S-Trimer binds to the ACE2 receptor with higher binding affinity than other S proteins produced,” said Liang.

Dynavax developed CpG 1018 to provide an increased vaccine immune response, which has been demonstrated in Heplisav-B. CpG 1018 provides a well‑developed technology and a significant safety database, potentially accelerating the development and large-scale manufacturing of a COVID-19 vaccine.

According to Liang, Clover is testing both Dynavax's CpG 1018 adjuvant and Glaxosmithkline plc's AS03 adjuvant. Both already have extensive clinical safety and efficacy track records. The GSK collaboration was announced in February.

“During pandemics like COVID-19, we believe adjuvants will play a critical role in the success of a potential vaccine, both by increasing vaccine efficacy as well as making vaccines more widely available by reducing the amount of antigen needed per dose,” said Liang.

Clover plans to initiate a phase I trial by the middle of 2020.

“Clover is currently developing the vaccine candidate and has the in-house manufacturing capability to deliver hundreds of millions of vaccine doses annually. As the program progresses, we will evaluate commercial partnerships, with the ultimate goal of making the vaccine as widely available as possible,” said Liang.

“Successfully responding to this public health emergency will require a collaborative approach, combining technologies and sharing data, in order to rapidly develop a vaccine to prevent COVID-19,” said Ryan Spencer, the chief executive officer of Dynavax. “We are proud to contribute to this global effort with the goal of supporting rapid development and enabling large-scale manufacturing through the utilization of CpG 1018, which has already been successfully implemented in an approved, marketed vaccine in the U.S.”

Dynavax is also contributing its CpG 1018 to the Coalition for Epidemic Preparedness Innovations (CEPI), a collaboration supporting the global effort to develop a vaccine to prevent COVID-19.

The initiative has led to a collaboration between Dynavax and the University of Queensland (UQ), Australia to develop a vaccine to prevent COVID-19 in early March.

UQ established their partnership with CEPI in January 2019 with the aim of developing a “molecular clamp” vaccine platform, which is a technology that enables targeted and rapid vaccine production against multiple viral pathogens.

CEPI has asked UQ to use its new rapid response technology, which allows for the rapid generation of new vaccines from the knowledge of a virus’s genetic sequence information, to develop a new vaccine against COVID-19. The race is on as many companies are also developing their own vaccines for the pandemic.

Besides the COVID-19 vaccine, Clover is focused on developing biologic therapies and has other projects in its pipeline.

“Currently, we have multiple programs in phase I-III clinical trials both in China and globally,” Liang said. “Our pipeline includes oncology (TNFSF trimer-fusion proteins), subunit-trimer vaccines (against RNA viruses), and Fc-Fusion proteins.”

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