Most commercialised vaccines protect against pathogens by stimulating the body to produce targeting antibodies. Live-attenuated or dead viruses are often used in vaccines, however, for some viruses, such as HIV and Ebola, these classical approaches are excluded for safety reasons. Instead of using viruses, virus-like particles (VLP) can be engineered to possess the same structural properties without being infectious. The main targets participating in developing immunity against viruses are glycoproteins located on their surface, which mediate attachment and fusion to the target host cells. A major advantage of the VLPs is their versatility, as multiple glycoproteins from the same or from different pathogens can be co-expressed on a single VLP. However, so far, VLPs have been manufactured by modifying individual viruses for each vaccine separately, i.e. a VLP for HIV, a different VLP for Ebola. The present generic platform provides a solution by generating a single VLP containing glycoproteins specific for a range of viruses.
The invention combines a core platform to generate virus-like particles (VLPs) and technology to incorporate viral glycoproteins of choice on the surface of the VLP. The novel approach to generate VLPs utilises matrix proteins of Mumps (MuV) or Parainfluenza 5 (PIV5) viruses, which display up to 2,000 viral fusion glycoproteins on their surface. Incorporating glycoproteins into VLPs, known as ‘pseudotyping’, involves fusing the viral glycoprotein of a chosen target (for example HIV-1 Env extracellular domain) to the transmembrane MuV or PIV5 fusion protein embedded within the VLP. The combination of these two steps enables generation of VLPs displaying multiple copies of the viral glycoproteins of choice (e.g. HIV-1, HPV).
Since the MuV and PIV5 viruses are unable to form VLPs by themselves, the incorporation of the membrane targeting sequence (MTS) helps with an effective viral particle release. When used as a vaccine, VLPs facilitate the production of protective antibodies against the target glycoproteins..