Projects

Stellabody® Technology in Infectious Disease – COVID-19 and beyond

An engineered antivirus decoy protein intercepts the docking module of the COVID-19 virus. The ACE2 viral entry receptor (shown in red) was fused to the Fc (blue) of human IgG1 to produce an antiviral decoy molecule which has bound to the receptor binding domain of SARS-CoV-2 (green). This interaction ‘neutralizes’ the coronavirus blocking it from finding its entry receptor (ACE2) on cells, so preventing infection. The Fc portion of the antiviral decoy engages our immune system to kill cells already infected with SARS-CoV-2, a scorched earth strategy that eliminates the virus from the body. Modelling by Dr Phillip Pymm


We have two major streams of translational research in this program.

Potent biologicals for the prevention and treatment of COVID-19

A lack of preparedness for the emergence of zoonotic coronaviruses led to the global health and economic catastrophe caused by the SARS-CoV-2 virus. We have generated novel biological drugs called ACE2-Fc that neutralise all SARS-CoV-2 variants and most importantly they will protect against many future coronavirus pandemics. ACE2-Fc is a fusion protein which was created from two naturally occurring but separate components. The first component is an engineered form of the human receptor for SARS-CoV-2, and other coronaviruses, called ACE2. The second component is the Fc portion of an antibody, that normally activates the immune system. By combining these two functions into one biological drug we can both prevent and treat COVID-19.


The complement subcomponent C1q, here resembling a cluster of 6 bent golf clubs, is the critical component of complement which recognizes target bound antibodies. The Stellabody® Fc portions form a hexameric cluster that is optimised for C1q binding and enhanced complement mediated cytotoxicity. C1q structure from Mortensen et al., (2017) Proc Natl Acad Sci U S A 114:986-991.

“Two-pronged” attack on the virus: First the ACE2 component protects healthy people because it neutralises the virus and prevents it entering cells where it would otherwise establish infection. Second the Fc component harnesses the normal immune system of the patient to kill the virus. By applying our Stellabody® technology we make these ACE2-Fc proteins potent activators of the immune system which then eliminate the neutralised virus to either prevent infection in healthy people or treat Covid-19-infected patients.

Most importantly, these biological drugs neutralise any coronavirus that utilise ACE2 for entry into cells – including those that arise in the future. These drugs will protect us against future pandemics of this type. We are presently adapting these drugs to be produced for clinical testing.

This work sets a precedent for the development of new treatments for major pandemic viruses and has broad implications for development of new treatments for protection against other major human infections.

Other Pathogens - Malaria and HIV


Stellabody® technology and mAbs are being directed against different pathogens, particularly malaria and HIV. Antibodies are important to neutralise microbes and the Fc which carries the Stellabody® technology is important for activation of the immune system to pathogens. We are seeking novel targets and new antibodies for a broader range of infections including hospital infection, antibiotic resistant microbes and emerging viruses to which we can apply the Stellabody® technology.

Results

Neutralisation of all SARS-CoV-2 variants; Stellabody™ enhancement of immune activation.

Collaborators

  • Prof Louise Burrell, University of Melbourne
  • Prof Stephen Kent, University of Melbourne
  • Dr Amy Chung, University of Melbourne
  • Dr Adam Wheatley and Prof Dale Godfrey, University of Melbourne
  • Prof Menno van Zelm, Monash University
  • Dr Wai-Hong Tham, WEHI
  • Prof Kanta Subbarao, Doherty Institute

Funding

  • Medical Research Future Fund
  • The State of Victoria COVID-19 Treatments Medical Research Fund

Contact Details

For any general enquiries relating to this project, please contact:

Professor Mark Hogarth

Head, Immune Therapies Group

Telephone

+61392822111

Email

mark.hogarth@burnet.edu.au