Broader applications of our technology

Broader applications of our technology

SpyBiotech’s proprietary technology has an exceptionally broad range of applications in vaccine development. The simple, efficient and irreversible reaction between the peptide SpyTag and its protein partner SpyCatcher provides unique opportunities to assemble vaccines against viruses, bacteria and parasites. Spy-based immunotherapy has also shown promise against cancer and chronic diseases. In the last few years, work at SpyBiotech and by academic groups around the world has generated important data on these diverse targets and different immunization platforms.

 

Viral diseases

In the context of viruses, SpyTag has been used for vaccine assembly for global challenges that have resisted standard vaccine approaches over decades, as well as for newly emerging viral outbreaks.

SpyBiotech is leading the development of a vaccine against human cytomegalovirus (HCMV), which is present throughout the world and is a major cause of deafness, blindness and neurological disabilities in babies.

SpyTag has been employed by leading groups at the NIH and Caltech towards a vaccine for HIV[1], [2].

SpyTag-based platforms were used to generate vaccine candidates for vector-transmitted viruses, such as Tick-borne encephalitis[3] and Zika Virus[4].

Most work has used Spy technology prophylactically, constructing vaccines, but recent work has shown that Spy-based nanoparticle assembly also has therapeutic potential, towards clearance of Hepatitis B Virus[5].

As soon as the SARS-CoV-2/Covid-19 outbreak started, academics began to use SpyTag-technology to move towards clinical testing of a vaccine.

 

Bacterial diseases

The bacterium E. coli is a great friend to molecular biologists in laboratory experiments, but certain strains of E. coli cause severe and life-threatening infections. Spy-based VLPs have induced effective antibodies in animal models to block the action of a toxin from dangerous strains of E. coli[6].

Spy-technology can be used on virus-like particles (VLPs) but also many other vaccine platforms: SpyTag facilitated the decoration of bacterial outer membrane vesicles (OMVs) to induce immune responses against Streptococcus pneumoniae, a globally significant pathogen which can cause death through pneumonia, meningitis or sepsis[7].

 

Parasite diseases

The academic founders of SpyBiotech have long worked towards the development of a malaria vaccine. Malaria is one of the hardest challenges in vaccine development because of the complexity of the parasite’s lifecycle, its genetic variability and the high level of antibody needed for protection. The earliest work on SpyTag using VLPs showed its potential for potent antibody induction against malaria, demonstrating responses to different life-cycle stages (pre-erythrocytic, blood-stage and transmission-blocking)[8]-[10].

Work against malaria showed how SpyTag-based vaccines induced higher quality antibodies in terms of their potential to protect from transmission of the disease[11].

 

Cancer and chronic disease

It is now clear that the immune system is key to fighting cancer. Recent advances have shown how taking the brakes off the immune system (using checkpoint-blocking antibodies) can reveal potent tumour-killing T cell responses. Also, identifying patient-specific genetic changes (a personalized medicine approach) can allow stronger immunity than responses against more general features of cancer.

Spy technology has shown its versatility in pre-clinical testing against large proteins expressed on the cancer cell-surface (e.g. HER2)[12], cancer-related peptides[8] , tumour-specific neoepitopes[13], or immune checkpoint proteins[9]. Such immune activation has led to both protective antibody and cytotoxic T lymphocyte responses[12],[13].

Spy-based targeting is also being developed against virus-induced cancer, caused by the Human Papilloma Virus (HPV)[14]. In the area of chronic disease, Spy technology has shown promise in pre-clinical models for immunotherapy of allergy[15].

 

Veterinary disease

Billions of animals around the world receive vaccines, including pets, horses and farmed animals. Many of these vaccines depend on inactivated or attenuated forms of the disease-causing organisms. This classic approach requires large-scale culture of pathogens that people would rather eradicate from the planet, as well as running the risk of attenuated pathogens regaining virulence.

The EU-funded Zoonoses and Anticipation Preparedness Initiative (ZAPI) is developing vaccine approaches for major veterinary and zoonotic challenges: Rift Valley Fever, affecting humans and livestock; Schmallenberg virus, which affects livestock; and MERS, a coronavirus from camels that caused a global outbreak in humans in 2012 (See link).

ZAPI has focused on the use of Spy-VLPs to enhance the future development of veterinary vaccines, to improve both the efficacy and speed of response.

 References

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