Out-licensing

Identification of Non Infectious Virus-Like Particles: Potential Applications as a Vaccine and as a Delivery System

Introduction/Background

Henderson Morley holds the rights to a vaccine technology known as L-particles and PREPS. Researchers at the Medical Research Council (UK) Institute of Virology in Glasgow discovered this technology.

Aims/Hypothesis

We are investigating the potential of light (L) particles of herpes simplex virus type 1.

Research

Researchers have discovered that herpes viruses in culture can be made to secrete equal quantities of live virus and of non-infectious particles that are identical in appearance to the live virus but lack viral DNA and surrounding protein shell (capsid). These particles, known as L-particles, are produced by all alpha-herpes viruses and can adsorb and penetrate host cells but are unable to replicate. They can be isolated to produce preparations that contain less than 1 per 100,000 contaminating virions.

This process has now been taken a stage further with the development of pre-viral DNA replication enveloped particles, known as PREPS. Unlike active viral particles (virions) and L-particles these are assembled prior to viral DNA replication and so contain no viral DNA or virions. The large scale production of PREPS will be possible by utilising recombinants, allowing a cheap and scaleable manufacture. Both L-particles and PREPS can serve as vaccines for the parent herpes virus from which they are derived. Because these particles are taken up by cells in the same way as the virus itself, they represent an ideal potential carrier to deliver therapeutic proteins into the cell, opening the prospect of enabling a wide range of novel intracellular therapeutic applications. Studies have already successfully applied this technology to glycoprotein B, the major immunognenic protein of human cytomegalovirus and CAT a non structural bacterial marker protein.

Henderson Morley has completed studies regarding its PREPS and L-particles vaccine platform. PREPS and L-particles were demonstrated to be stable, safe, and well tolerated. The studies also demonstrated that a potent and dose related immune response was generated to the target antigen. These positive results will now lead to further studies examining engineered PREPS and L-particles targeted at either cancer or other model antigens. These studies will aide the further development of PREPS and L-particles as cancer immunotherapeutic candidates. The studies will also aide with identification and selection of lead candidate vaccines. These technologies are being developed to target a number of important diseases including virus infections in humans such as Cytomegalovirus, Epstein Barr virus and herpes simplex virus, and as a cancer immunotherapy for a wide range of different forms of human and animal cancers.

Henderson Morley has started preclinical toxicity, immunogenicity and dose ranging studies using PREPS and L-particles as a vaccine candidate for herpes simplex virus (HSV). These studies will demonstrate a further opportunity for the PREPS and L-particles vaccine platform in an important disease area. A successful vaccine against HSV diseases would have significant market potential.


Conclusion

The ability of PREPS and L-particles to replicate viral forms in a non-infective way suggests that they provide a novel, safe and versatile vehicle for vaccination in both humans and animals. Whilst PREPS may be useful as herpes virus vaccines, they may also have potential for delivery of therapeutic neuropeptides expressed under the control of suitable viral promoters engineered into the virus stock, as they are anticipated to exhibit normal herpesvirus cell tropism.

Relevance/Opportunity

Henderson Morley has patents on the technology is seeking partners to take the concept forward into full clinical development. A development partner is sought to undertake the further clinical development of PREPS and L-particles as vaccines and protein delivery vectors. Henderson Morley will consider a variety of partnering options.

Preclinical