EXPERTS IN INSECT, MAMMALIAN AND BACTERIAL EXPRESSION
Research and development from OET
Oxford Expression Technologies (OET) Ltd are experts in Baculovirus protein expression and leaders in global research and development within the biotechnology and pharmaceutical industry. We are also home to the flashBAC™ baculovirus expression kit. Take a look at some of our R&D below and get in touch for further information.
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Development of an economically viable Crimean Congo haemorrhagic fever virus vaccine for local production
Crimean Congo haemorrhagic fever (CCHF) virus causes a severe disease that outbreaks sporadically in Africa, the Balkans, the Middle East and Asia. The disease is spread through tick bites or contact with virus-infected animals causing multiple symptoms including liver and kidney damage. Unfortunately, less developed countries are poorly equipped to deal with this type of disease.
The CCHF virus is a hazardous pathogen requiring high containment facilities to produce inactivated or attenuated vaccines. Although such vaccines can be derived, they have been shown to have toxic side effects. This project plans to use information about the genetics of the CCHF virus to design a synthetic gene that has the code for making protein components of the virus that can stimulate production of protective antibodies. An insect baculovirus will be used to make the CCHF virus proteins. These proteins will be tested to determine their suitability as a candidate for use as a sub-unit vaccine.
Another aim of this project is to develop CCHF vaccines that can be produced locally, where they are needed – using simple technologies. The technology we develop will also be readily transferable to make virus vaccines for a number of other diseases.
This research was funded by the Department of Health and Social Care as part of the UK Vaccine Network (UKVN), a UK Aid programme to develop vaccines for diseases with epidemic potential in low and middle-income countries (LMICs)
SARS-COV-2 (COVID-19 virus) research
OET is currently helping COVID-19 research efforts by producing the recombinant spike glycoprotein of SARS-CoV-2 for clients. The protein will be used for further research, diagnostics and potential vaccine production.
OET is also engaged in in-house COVID-19 research and is working on an insect cell-based vaccine using our flashBAC system enabled through funding from Innovate UK/Department of Health through the Vaccines for Global Epidemics: development and manufacture initiative.
OET has recently received further funding from Innovate UK for their collaboration with Vaxine Pty Ltd for the development of a COVID-19 vaccine.
OET is working in collaboration with Oxford Brookes Insect Virus Research Group on an exciting new project; NanoZoo. This project aims to use the baculovirus expression system to produce surface antigens of viral pathogens of farm animals (chickens and pigs) to develop novel vaccines.
Novel vaccine platforms are urgently needed to produce efficacious, safe, low cost, and rapidly adaptable (‘plug-and-play’) vaccines to face the threat of zoonotic viral diseases in livestock. Protein nanoparticle vaccines, e.g. the highly successful porcine circovirus and the human papillomavirus vaccines, are generally considered an optimal vaccine format because of their high efficacy and intrinsic safety. Built on our success with clinical testing of a nanoparticle vaccine against covid-19 (H2020 Prevent-nCoV, clinical trial COUGH-1), the aim of the NanoZoo project is to apply our unique protein nanoparticle vaccine platform for rapid response against zoonotic viruses in poultry and swine. This technology involves expression of viral antigens in insect cells combined with antigen presentation on protein nanoparticles to induce a superior immune response. In the NanoZoo project, this approach will be applied for developing novel vaccines against two important zoonotic viral diseases in poultry (Avian influenza virus and Newcastle disease virus) and two emerging vector-borne zoonotic viral diseases in swine (Japanese encephalitis virus and Getah virus). Viral glycoproteins, or immunodominant subunits thereof, will be expressed in insect cells using the robust baculovirus expression system to ensure correct folding and glycosylation of the antigen. The viral antigens will then be coupled onto protein nanoparticles to be evaluated in vaccination-challenge studies in animal models (chicken and mice). The baculovirus expression system will be engineered as a very fast ‘plug-and-play’ platform to go in a single step from a synthetic gene to viral antigen production, which will outcompete novel mRNA vaccine platform technologies in terms of speed, volume and cost. The project brings together academic and industry experts in viral antigen expression, nanoparticle vaccines and animal health.
BBSRC STFC Facility Access Funding
Baculovirus expression vectors (BEVS) have become one of the most versatile and successful systems for the production of recombinant proteins. Frequently, they succeed in producing difficult targets where other systems have failed. Increasingly, they are employed to produce recombinant protein subunit vaccines, e.g. influenza, Covid-19 and several for animal diseases. They are also very useful for producing large, complex transmembrane proteins for drug discovery.
The natural replication cycle of baculoviruses in insect cells involves early, late and very late phases of gene expression. Notably, the late phase sees the production of infectious virus particles that bud from the plasma membrane and are essential for virus dissemination in cell culture. Recombinant proteins are largely produced in the very late phase, however, some protein synthesis initiates in the late phase and if the target is cytotoxic this can have an impact on budded virus (BV) yield. This may reduce the infectious titre of virus by up to 10-fold. While this is not usually a problem in small scale tests to monitor recombinant proteins, it can have serious consequences in subsequent scale up work where large cultures of insect cells are infected with BEVS using high particle:cell ratios. A further issue is the production of BV stocks with high titres that may not be stable upon storage. Rather than maintaining a high titre for months, this period reduces to a few weeks of storage in a cold room.
The cause(s) of the virus low titre and instability are unknown, apart from the link with recombinant protein production. We hypothesise that the structural integrity of BV is affected by the recombinant protein. However, BV structural data is very scarce due to limited access to state-of-the-art facilities, leading to a lack of in-depth understanding of these expression vectors and impacting on further BEVS development. With world-leading structural-characterisation facilities at STFC, such as SANS and cryo-TEM, we can examine and investigate the structural integrity of recombinant BV with compromised infectious titre or stability on storage.
The successful completion of this structural study will allow us to formulate intelligent design strategies for recombinant protein production that mitigate their effect on BV structure and infectivity.