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Molecular Clamp: a Novel Protein Vaccine for Influenza, RSV, Ebola and Other Human and Veterinary Viruses
UniQuest Pty Ltd Australia flag Australia
Abstract ID:
Molecular Clamp technology is the basis of a novel subunit vaccine for class I and III enveloped viruses. It stabilizes the pre-fusion form of viral fusion proteins to mimic the protein conformation found on live virus, exposing highly neutralizing epitopes. POC studies have
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All enveloped viruses, such as influenza virus and respiratory syncytial virus (RSV), require fusion of viral and host cell membranes to enter and infect the host cell. Viral fusion proteins facilitate this by undergoing structural rearrangements from a metastable ‘pre-fusion’ conformation to a highly stable ‘post-fusion’ conformation.

Viral fusion proteins are excellent subunit vaccine candidates for many medically important enveloped viruses as they are the primary targets of protective neutralizing antibody responses. However the intrinsic unstable nature of fusion proteins is a major obstacle for effective subunit vaccine design.

For vaccines, the pre-fusion form of the viral fusion protein is more desirable. Studies have shown the pre-fusion form of viral envelope fusion proteins contain important epitopes (not present on the post-fusion form) that produce broadly cross-reactive and potently neutralizing antibodies as part of a strong immune response.

Traditional approaches to recombinant expression of viral fusion proteins typically result in premature triggering and a conformational shift to the structurally more stable post-fusion form.

Description of Technology
Molecular Clamp technology addresses the industry need to produce stabilized recombinant fusion proteins that remain substantially in their pre-fusion form. It uses a polypeptide moiety as a molecular clamp and has been shown to have increased stability over alternate stabilizing trimerization domains such as Foldon and GCN4.

Used as the basis of a novel protein vaccine, the molecular clamp technology is designed to elicit a protective immune responses against class I and III enveloped viruses of human and veterinary importance.

The clamped pre-fusion protein can also be used as an antigen in an antibody drug discovery program.

The Molecular Clamp approach is a platform technology. Researchers at The University of Queensland have already used it to produce chimeric polypeptides that mimic the pre-fusion conformations of influenza, RSV, HIV,
measles virus and Ebola virus.

Data has shown the Influenza HA Clamp has strong reactivity with known protective monoclonal antibodies (C05, CR8043, FI6V3). It induced a more potent neutralizing immune response compared with current vaccine FluQuadri® (Sanofi Pasteur) and was found to be ~80-fold more cross-reactive antibody to heterologous strains (including avian H5N1).

Data with other viruses includes Ebola which induced a potent neutralizing immune response comparable with rVSV-ZEBOV (Merck). Further, the Molecular Clamp protein vaccine was shown to be heat stable with no loss in
antigenicity after two weeks at 37°C.

Market Potential
In 2014, the value of the world market for vaccines was estimated at US$33 billion with the HIV market valued at US$14 billion and influenza market at US$4 billion. 

As well as these and other applicable viruses of human importance, such as herpes virus, mumps and measles, the technology can also be applied to veterinary applications including bovine ephemeral fever virus (BEFV), bovine RSV, Hendra virus, Newcastle Disease virus and canine distemper virus.
Type of Business Relationship Sought
UniQuest is seeking licensing, collaborative or investment partners to commercialise the technology
Last Updated Apr 2017
Technology Type PLATFORM
Phase of Development PRECLINICAL


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