A second chance for UQ's molecular clamp vaccine platform

The University of Queensland (UQ) is set to take a second-generation ‘molecular clamp’ vaccine to a proof-of-concept human trial, after the Coalition for Epidemic Preparedness Innovation (CEPI) announced it would provide up to AU$8.5 million to support further development of the technology. The money will fund Phase I testing of the technology for potential use in the global response to future disease outbreaks, including outbreaks caused by novel pathogens.

The molecular clamp technology works by ‘locking’ viral proteins — involved with infection and cell entry — into a shape that allows for an optimal immune response. This process requires the sequence of the viral protein, which can be determined from its genome and is then coupled with an optimised ‘clamp’ sequence; the resulting synthetic antigen can then be purified and rapidly manufactured into a vaccine. Before the invention of this technology, locking the shape of viral proteins was very difficult to achieve.

CEPI first entered into a partnering agreement with UQ in January 2019, announcing up to US$10.6 million to develop a molecular clamp platform that would enable targeted and rapid vaccine production against multiple viral pathogens. In January 2020, CEPI asked the UQ team to begin testing the technology against SARS-CoV-2. Clinical testing of UQ’s vaccine candidate was underway by July 2020, which provided positive safety and immunogenicity data.

Unfortunately, UQ scientists discovered that a constituent of the vaccine candidate also resulted in diagnostic interference with some HIV tests — an unforeseen cross-reaction — and so decided to halt further development of their COVID-19 vaccine candidate. Because it would not have been suitable for broad deployment, the team decided at that point not to progress the COVID-19 vaccine candidate into Phase II/III clinical trials.

Nevertheless, CEPI believed that the concepts underlying UQ’s molecular clamp technology showed promise. It continued to support the UQ team to resolve the issue of diagnostic interference so that the platform could be developed for use against other diseases in the future, potentially within 100 days of a new virus emerging.

Now, following months of research, Associate Professors Dan Watterson and Keith Chappell, together with the UQ clamp vaccine team, have successfully re-engineered their molecular clamp technology and demonstrated its promise and safety in laboratory testing. The team has also designed a second-generation version of their SARS-CoV-2 vaccine using this upgraded technology and will soon begin Phase I testing to demonstrate safety and benchmark immunogenicity against approved COVID-19 vaccines.

“We have been able to validate the Clamp2 platform in the laboratory and show that it is equivalent to the original platform across multiple virus families including influenza virus, Nipah virus and SARS-CoV-2,” said Chappell, the leader of UQ’s Rapid Response Vaccine Pipeline. “Preclinical testing had shown the Clamp2 platform was meeting all expectations, producing stabilised antigens and inducing strong neutralising immune responses.

“Importantly, this re-engineered technology does not pose any issue with diagnostic interference as was encountered in 2020.”

The clinical batch of the Clamp2 vaccine will be manufactured at the Queensland node of the National Biologics Facility (NBF), housed within UQ’s Australian Institute for Bioengineering and Nanotechnology. Ben Hughes, Interim Director of NBF, said it was a significant achievement that a pivotal proof-of-concept trial would be conducted with material produced at UQ — although Watterson, who spearheaded the successful redesign, emphasised that the ultimate aim was not to rush a new COVID-19 vaccine to market.

“This is about the role this technology could play in safeguarding against future pandemics, and ensuring we have an Australian-based rapid response vaccine pipeline and the team and infrastructure ready to deliver clinical-grade material should it be needed in the future,” Watterson said.

“Having this capability in Queensland complements planning for a new translational manufacturing facility at the TRI [Translational Research Institute], a facility that will support future efforts to progress therapeutic and vaccine candidates through the clinical trials process and to market.”

Queensland Deputy Premier and State Development Minister Steven Miles said the state government invested $10 million to help UQ develop the molecular clamp platform, which was described as having the potential to become a global game changer. Additional support was provided by the community and philanthropic partners including the Paul Ramsay Foundation, BHP Foundation, Newcrest, Glencore, RACQ and its members, A2 Milk, The Lott and Aurizon.

Dr Melanie Saville, Executive Director of Vaccine R&D at CEPI, said the UQ team demonstrated “true grit and the power of the scientific process to yield tangible advances in vaccinology”, which could provide the world with “an invaluable tool to rapidly respond to future pandemic threats”. In line with CEPI’s equitable access policy, UQ has agreed that vaccine candidates produced using the platform technology will be available in an outbreak situation to populations at risk including in low-income and middle-income countries.

“CEPI is now implementing its $3.5 billion pandemic plan, which includes substantial investments in multiple platform technologies,” Saville said. “These investments will help the world respond to the next Disease X and compress vaccine development timelines down to 100 days, so that we can mitigate the devastating economic and human costs of epidemic and pandemic diseases.”

Image caption: Associate Professor Keith Chappell, leader of UQ’s Rapid Response Vaccine Pipeline.

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