We are creating some awesome events for you. Kindly bear with us.

UQ researchers validate clamp tech

University of Queensland scientists have published the clinical trial data confirming their molecular clamp-stabilised vaccine technology was safe and potentially effective. The vaccine candidate developed by the team last year did not progress through to Phase 2/3 clinical trials, due to cross-reactivity caused by the protein fragment used to stabilise the clamp design.

Initial data from the clinical trial conducted in Brisbane was initially released last December and has now been published following peer review in the prestigious Lancet Infectious Diseases. Project co-leader Associate Professor Keith Chappell said 99% of vaccinated participants in the study produced a neutralising immune response.

“In 75 per cent of vaccine recipients it was above the average in recovered patients, and in 38 per cent it was more than twice the average for recovered patients,” he said. “Adverse events were comparable to those in the saline placebo, with the only exceptions being mild injection site pain and tenderness.”

Project Director Professor Trent Munro said the paper also discussed the cross-reactivity in HIV diagnostics that led to the decision not to proceed into later-stage clinical studies. “The design of the original molecular clamp excluded known antibody binding sites to reduce the potential, but unfortunately the antibodies registered a low response on some highly sensitive HIV tests.”

Project co-leader Professor Paul Young said the 2020 vaccine candidate was not an option for Australia’s current vaccine rollout. “The team understood the decision in December to shift the focus to other candidates that were showing promise. Some of these vaccines are now in the market and need to remain the immediate priority.”

It was noted that the study has strongly validated the Molecular Clamp technology as a promising rapid response strategy for vaccine development. “The team is continuing to work on alternative clamp constructs that could be used to respond to COVID-19 in the future or other viral diseases.”

The data published relates to the clinical trial involving 120 participants aged 18 to 55, 96 of which received the vaccine candidate. Collaborators on the clinical trial included CSL/Seqirus, Australian National University, Doherty Institute, CSIRO, Patheon, Cytiva and Nucleus Network.

In addition, to support from the Coalition for Epidemic Preparedness Innovations (CEPI), the Queensland Government provided $10 million Advance Queensland funding for the vaccine project last year, the Federal Government contributed $5 million and more than $10 million was provided by philanthropic and other donors.

The research is published in Lancet Infectious Diseases.

What is clamp-stabilised vaccine technology?

molecular clamp is a polypeptide used to maintain the shape of proteins in some experimental vaccines. On a virus, pre-fusion proteins on their surface provide an attractive target for an immune reaction. However, if these proteins are removed or made by recombinant technology, they lose their shape and form what is called a “post-fusion form”.

When part of a virus, these proteins maintain their form by forming a quaternary structure with other viral proteins. The pre-fusion state of the protein is a higher energy metastable state. The extra energy is used to overcome the activation barrier of the fusion to the cell membrane. The virus protein (or part of it) in combination with the clamp polypeptide is called a chimeric polypeptide.

The clamp is made from amino acid residues in a pattern that repeats after every seven residues and must be at least 14 residues in length. The clamp self-assembles into a twin helix with one strand going forward and the other in reverse.

The pairing of the amino acids in the strands is ensured by a pattern of hydrophobic and hydrophilic amino acids. The pattern is arranged so that none of the clamps will bind to the protein from the virus. The clamp self-assembles into a stiff rod. The clamp is linked to the desired part of the virus protein by a linker. The linker may serve other functions, such as allowing the chimeric protein to be purified from a mixture.

Send this to a friend